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A Historical Perspective on Garlic and Cancer
Abstract
Epidemiological and laboratory studies provide insight into the anticarcinogenic potential of garlic and its constituent compounds. Both water- and lipid-soluble allyl sulfur compounds are effective in blocking a myriad of chemically induced tumors. Part of the protection from these compounds probably relates to a block in nitrosamine formation and metabolism. However, blockage in the initiation and promotion phases of the carcinogenicity of various compounds, including polycyclic hydrocarbons, provide evidence that garlic and its constituents can alter several phase I and II enzymes. Their ability to block experimentally induced tumors in a variety of sites including skin, mammary and colon, suggests a general mechanism of action. Changes in DNA repair and in immunocompetence may also account for some of this protection. Some, but not all, allyl sulfur compounds can also effectively retard tumor proliferation and induce apoptosis. Changes in cellular thiol and phosphorylation stains may account for some of these antitumorigenic properties. The anticarcinogenic potential of garlic can be influenced by several dietary components including specific fatty acids, selenium, and vitamin A. Since garlic and its constituents can suppress carcinogen formation, carcinogen bioactivation, and tumor proliferation it is imperative that biomarkers be established to identify which individuals might benefit most and what intakes can occur with ill consequences..
... Its leaves are usually used for cooking in the seasoning of meat and fish [1]. It is also used to protect body organs against carcinogenesis [5,6] and can act as a botanical insecticide [7]. ...
... Sci. 2023, 13 1,3,4,5,6,7,8,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41 ...
... Components present in: Leaves: 1, 3, 4, 5, 6,7,8,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41 The n-hexane fraction derived from L. nobilis leaves has been found to have a neuroprotective effect. Specifically, it has been shown to significantly decrease the generation of reactive oxygen species (ROS) in human neuroblastoma SH-SY5Y cells that were induced by dopamine (DA) in vitro. ...
Laurus nobilis belongs to the family Lauraceae and is characterized by its evergreen nature. It is well known because of its traditional use in cooking and folk medicine. Many studies have been performed regarding its chemical composition and the pharmacological potential it exhibits. It has been reported to have antioxidant, antibacterial, antifungal, antiviral, biocidal, antidiabetic, antiulcerogenic, neuroprotective, analgesic, anti-inflammatory, and anticholinergic properties, making this plant of great clinical importance. The main chemical compounds that show bioactive properties in L. nobilis are terpenoids, phenolics, and fatty acids. The purpose of this review is to describe the main use of L. nobilis, notably of the leaves and fruits, and to relate their metabolite content with their pharmacological and toxicological properties.
... It has activities against liver damage (Stratton et al. 2000). Essential oil also shows potent hepato protective activity mainly on chemo preservation during the initiation stage that induces phase I or II drug metabolizing enzymes to prevent liver damage (Milner 2001). ...
... Mainly, in essential oils extracted from garlic there is a rich source of volatile organosulfur component. Due to their activity in modulating phase I & II drug detoxifying enzymes, they are a group of potential cancer chemopreventive agents (Milner 2001). The organosulphur components of garlic oil are of three types i.e., diallyl trisulfide (DATS), diallyl sulphide, diallyl disulphide (DADS). ...
Essential oils (EOs) are natural products obtained from different parts of a plant, such as flower, leaves, stems, fruits, seeds, roots, barks, or resin. It represents an important part of traditional pharmacopeia practices in healing of human ailments. It is used as raw materials in cosmetics, spices, foods, perfumes, and in treatment of several health disorders. There are several methods for extracting EOs from plants. They are the methods like hydro-distillation, steam distillation, hydro diffusion and cold pressing to name a few. The use of EOs as antimicrobial and pharmaceutical agents for curing various diseases has gained a considerable attraction of researchers in recent times. The complex mixture of EOs and their constituents have been reported to inhibit human pathogens, insects, and another harmful organism. The current review focusses on the chemical bioactive components of EOs, methods of extraction, chemical constituent, different plants as source of extraction and its application towards the treatment of various diseases in our day to day life, in vivo validation of essential oil, nanoformulation of essential oils.
... Many authors, like Dirsch et al. [12], Shirin et al. [13], and Sigounas et al. [14], have recorded that Garlic contains several organosulfur compounds, the most biologically active of which is allicin, which stops the growth of cancer cells and causes malignant cells from various tissue sources to undergo apoptosis. Garlic has been shown by several authors to lower the risk of cancer when consumed regularly, and its organosulfur molecule has been shown to be beneficial in preventing experimentally produced cancers in a variety of organs, including the skin, uterus, colon, and breast [15,16]. Many authors noted that allicin has multiple action such like antibacterial, antiviral, and antiparasitic effects [17]. ...
According to the World Health Organization, cancer is the foremost cause of mortality globally. Various phytochemicals from natural sources have been extensively studied for their anticancer properties. Allicin, a powerful organosulfur compound derived from garlic, exhibits anticancer, antioxidant, anti-inflammatory, antifungal, and antibacterial properties. This review aims to update and evaluate the chemistry, composition, mechanisms of action, and pharmacokinetics Allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells. Safety and clinical aspects are meticulously scrutinized, providing insights into the tolerability and adverse effects associated with allicin administration, along with an overview of current clinical trials evaluating its therapeutic potential. In conclusion, this review underscores the promising prospects of allicin as a dietary-derived medicinal compound for cancer therapy. It emphasizes the need for further research to elucidate its precise mechanisms of action, optimize delivery strategies, and validate its efficacy in clinical settings.
... Além disso, possui diversas vitaminas, tais como: A, B2, B6, C, aminoácidos, ferro, silício, iodo, enzimas e a alicina, podendo ser utilizado no tratamento de doenças causadas por bactérias e fungos. Schineider (1984) afirma que o alho contém alicina, um líquido amarelado que aparece após a trituração ou o corte do alho, sendo responsável por parte das propriedades farmacêuticas da planta (Kik & Gebhardt, 2001), afirmam que a planta de alho pode ser bem aproveitada, sendo que as folhas e as inflorescências devem ser consumidas ainda verdes e os bulbos devem ser destinados aos condimentos alimentares e para medicamentos fitoterápicos em função dos efeitos atribuídos aos compostos sulfurados, abundantes nos tecidos desta espécie (Lorenzi & Matos, 2002), citam que o alho é constituído por cerca de 30 substâncias de uso farmacêutico, sendo que o bulbo apresenta rendimento aproximado de 0,1 a 0,2% de óleo volátil de acordo com (Milner, 2001). ...
RESUMO O objetivo deste trabalho foi testar a utilização de produtos naturais utilizados na profilaxia e no tratamento de lesões e enfermidades de reprodutores de peixes, como tratamento alternativo aos medicamentos alopáticos. Foram utilizadas a casca da aroeira Schinus terebenthifolius, a casca do alho Allium sativum e o sal comum, cloreto de sódio (NaCl) no com base nas suas propriedades antimicrobianas para usos profiláticos em peixes. Os animais foram mantidos em caixas d'água com capacidade de 1000L, com fluxo de água contínuo para oxigenação e renovação. A densidade de estocagem foi de 3 peixes/m³, densidade baixa, visto que os peixes estavam próximos da época de reprodução, quando apresentam comportamento territorialista, com confrontos entre machos, ocasionando perda de escama nos indivíduos, se concentrando principalmente em cima da linha lateral. O tratamento teve a duração de 21 dias. Diariamente pela manhã e à tarde foram aplicados um banho na pirapitinga Piaractus brachypomus em solução de cloreto de sódio a 30g/L por 30 segundos, depois foram aplicados diretamente o extrato de aroeira (50 mL do concentrado, sem diluição) e extrato de alho, diluído(40 mL em 60 mL de água), aplicado diretamente na lesão. Palavras-chave: Piscicultura, tratamentos alternativos, extrato de aroeira, extrato de alho, cloreto de sódio. ABSTRACT The aim of this research was to test the use of natural operating as prophylaxis for the treatment of injuries and diseases during fish reproduction at aquaculture stations as an alternative treatment to allopathic medicines. The main objective was to analyze the mastic bark (Schinus terebenthifolius), garlic bark (Allium sativum), and sodium chloride (NaCl) regarding their antimicrobial properties for prophylactic use. The broodstocks of the species pirapitinga Piaractus brachypomus were kept confined in water tanks with a capacity of 1000 L, with a continuous water flow for oxygenation and renewal. The stock density was 3 fish/m³, due to the fish being the breeding season why it becomes territorial. A confrontation between males occurred, causing the loss of scales in one of the specimen, mainly above the lateral line. The treatment of this injured fish lasted for 21 days, daily in the morning and afternoon; it was bathed in a 30g/L salt solution for 30 seconds, then the mastic and garlic extract were applied directly to the injury. For the mastic extract 50 mL of the concentrate was used without dilution and for the garlic extract 40 mL was diluted in 60 mL of water. INTRODUÇÃO Vários produtos naturais são utilizados popularmente por apresentam propriedades medicinais, como por exemplo, cascas, folhas, raízes e frutos, considerados como adstringente, antidiarreico, anti-inflamatório, depurativo, diurético e febrífugo. Esses produtos são empregados no tratamento da diarreias, inflamações, para promover a transpiração e a eliminação de líquidos. Dentre eles, destaca-se a casca da aroeira Schinus terebenthifolius tem ação contra febre, hemoptises e afecções uterinas, em geral. Da casca, extrai-se óleo
... For thousands of years, garlic has been utilized in numerous cultures for both culinary and medical applications (Rivlin 2001). It has been proven that garlic reduces the risk of heart disease as well as exerts anticarcinogenic effect against a variety of cancers (Orekhov and Grünwald 1997;Milner 2001;El-Bayoumy et al. 2006). Garlic (Allium sativum) is a food used as a flavor and a natural therapy. ...
Scientists are seeking to find an effective treatment for tumors that has no side effects. N-Acetyl-l-cysteine (NAC) is a thiol compound extracted from garlic. Current study explores the potential of NAC-loaded niosomes (NAC-NIO) for tumor treatment in mice. NAC-loaded niosomes’ efficiency, morphology, UV absorption, size distribution, zeta potential, release, and FTIR analysis were evaluated. For vivo study, 25 male BALB/c mice were divided to five groups: gp1 negative control (receive saline), gp2 positive control (tumor group), gp3 treated with NAC, gp4 treated with NAC-NIO at the same time of tumor injection, and gp5 treated with NAC-NIO after tumor growth (day 14). The impact of NAC-NIO on the tumor treatment was evaluated by measuring tumor size progress, comet assay, oxidative stress parameters (GSH, nitric oxide, MDA), western blot analysis, and histopathological investigation of tissues. NAC-NIO showed 72 ± 3% encapsulation efficiency and zeta potential − 5.95 mV with spherical shape. It was found that oral administration of NAC-NIO in a dose of 50 mg/kg provided significant protection against tumor cells. Our formulation decreases DNA injury significantly (P < 0.05). It was noticed that NAC-NIO can increase oxidative stress levels in tumor tissue. On the other hand, the caspase 3 and caspase 9 gene expression were upregulated significantly (P < 0.001) in mice administrated NAC-NIO compared with all other groups. Histological studies confirmed the protective effect of NAC-NIO against tumor especially for treatment during tumor growth protocol. The results suggested that oral delivery of NAC-NIO formulation improved antioxidant effect.
... The plant Allium sativum belongs to the Amaryllidaceae family 16 . Other studies discuss the function of the most effective Allium sativum compound, Allicin, and its antitumor properties against breast and prostate cancer are demonstrated. ...
Cancer is the world's second-largest cause of death. Although substantial progress has been made in treating and controlling cancer progression, there are still significant flaws and space for improvement. During chemotherapy, several unfavourable side effects might arise. Natural-derived substances are attracting scientific and academic attention since they are thought to have fewer hazardous side effects than conventional treatments like chemotherapy. Natural secondary metabolites produced by plants are being studied for their anticancer properties, which could lead to the creation of novel therapeutic medications. The demand for naturally produced chemicals from medicinal plants and their features that make them possible anticancer treatments are discussed in this review.
... Its bulb has a yield of 0.1 to 0.2% (v: p) of volatile oil, standing out in its chemical composition diethyl disulfide, allyl disulfide, diallyl disulfide, allyl trisulfide, diallyl polysulfide, S-allyl cysteine, S-allyl cysteine, S-allylmercaptocysteine, among other constituents. The sulfur compounds present in garlic are in quantities three times higher than those of other vegetables also rich in these compounds, such as onions and broccoli (MILNER, 2001). The type and concentration of compounds extracted from garlic depend on its stage of maturation, cultivation practices, location in the plant, conditions of processing, storage and handling (MARCHIORI, 2003). ...
Garlic is a horticultural plant of excellent spice, nutritional and herbal value. The conditions to which vegetables are subjected in minimal processing can result in a series of important physiological changes, caused by mechanical damage suffered in the transformation steps. The control chart or chart is a statistical quality tool, which aims to identify deviations and point out possible failures in the production process. Therefore, the work aimed to implement control charts in a company that produces garlic paste. Analyses of the colorimetric parameters L, *a and *b, pH, moisture and ash were made for 20 samples of crushed garlic paste, where it was stored in drums, then 20 grams of garlic paste were collected in 10 different points of each drum. The graphs were assembled with the determined control limits and the results obtained were analyzed. For all analyses the processes were under control, were predictable and stable, except for the colorimetric parameter *a, where a sample exceeded the determined control limit making the process out of control.
... The bioactive compounds changes lipid peroxidation, nitric oxide synthase effect, nuclear factor-kB, EGFR and protein kinase C [70]. Several studies have shown that Allium sativum and its organosulfur constituents decreases the risk of breast, larynx, colon, skin, endometrial, esophageal, bladder and lung cancers with proven anticancer effects in breast and prostate cancers [71][72][73][74][75]. b) Onion (Allium Cepa): herbaceous biennial plant, is the most widely cultivated species of the Allium genus. ...
Plants have played significant roles in the management of diseases in ancient times, and folk medicine. And, they still play large roles among natives in rural communities and in parts of Africa and Asia. Up to 60% of drugs in use today have their origin to plants and natural products. Several of the known plants used for management of various ailments in the past have reported wide ranges of pharmacological effects which include antioxidant, anti-inflammatory, antimicrobial, antiallergic, immunomodulatory etc. effects, due to their multiple bioactive phytochemical constituents. Some of these plants equally exert dual-effect antidiabetic-anticancer activities by affecting processes and pathways common to both diseases viz. antioxidant, anti-inflammation, anti-hyperglycemia, increase in insulin sensitivity, decrease in insulin resistance and modulation of diabetes-cancer common and related signal transduction pathways. They equally exert direct antidiabetic and anticancer effects by inhibiting enzymes involved in glucose metabolism, and mediating anti-tumor processes like apoptosis, antiproliferation, antimigration, antimitosis, antiangiogenesis etc. These plants have been shown to be effective either as monotherapy or in combination with conventional therapies where they exert syner-gistic properties and increased activities. This article reviewed several plants with reported proven and potential dual-effective antidiabetic-anticancer properties , their bioactive constituents and pharmacological processes, their reported in vitro and in vivo studies, and proffer insights on their new roles, challenges and prospects.
... Nitroso compounds, among them polycyclic aromatic hydrocarbons and heterocyclic amines formed during food preservation, and cooking have beneficial anticarcinogenic activities [14]. The chemical carcinogenesis is also inhibited by allyl sulfur compounds such as diallyl sulfide [15,16], isolated from garlic. The doubleedged curcumin is known for its cancer-preventive effect [17]. ...
Abdominal organs (liver, kidney, spleen) are frequent targets of cancer cell invasion but their primary tumours are less known for their metastatic potential to other organs e.g. to the breast. Despite the known connection of the pathogenesis from breast cancer to liver metastasis, the study of the spread in the opposite direction has been neglected. The notion that breast cancer could be a metastasis besides being a primary tumour is based on rodents’ tumour models upon implantation of tumour cells under the capsule of the kidney or under the Glisson’s capsule of the liver of rats and mice. Tumour cells develop into a primary tumour at the site of subcutaneous implantation. The metastatic process starts with peripheral disruptions of blood vessels near the surface of primary tumours. Tumour cells released into the abdomen cross the apertures of the diaphragm, enter the thoracal lymph nodes and accumulate in parathymic lymph nodes. Abdominal colloidal carbon particles injected into the abdomen faithfully mimicked the migration of tumour cells and deposited in parathymic lymph nodes (PTNs). An explanation is provided why the connection between abdominal tumours and mammary tumours escaped attention, notably, parathymic lymph nodes in humans were referred to as internal mammary or parasternal lymph nodes. The apoptotic effect of Janus-faced cytotoxins is suggested to provide a new approach against the spread of abdominal primary tumours, and metastatic development.
... It is an important and widely cultivated plant used as a food flavoring agent and it also has several medicinal applications. The active compounds show antibiotic, antitumor, cholesterollowering, and antithrombic effects [14]. Caladium is an im-portant group of ornamentals. ...
Somatic embryogenesis has been employed in various basic and applied studies such as cellular differentiation of plants, generating transgenic en masse and for mass propagation of elite, endangered and ornamental plants. The studies undertaken in some monocot genera (Eucharis, Hippeastrum, Crinum, Caladium, Gloriosa and Allium) suggest that in vitro embryogeny may also help in establishing relationship among plants, plant groups of similar or dissimilar history. The investigated plants are a few representative monocotyledonous genera, belonging to closely-related families in which in vitro embryogenesis was studied. The observations indicated that Eucharis and Hippeastrum, member genera of the family Amaryllidaceae showed similarity, while Crinum of the same family showed dissimilarities in in vitro em-bryogeny. In these investigated monocot plants, secondary embryo formations were not observed on primary embryos. Beside embryo ontogeny, the structure and development of embryo, some degrees of similarities in the requirement of plant growth regulator (PGR), especially the BAP's participation (2.22-4.40 µM) in embryo formation, presence of embryo dormancy was also noted. The scanning electron microscopy of embryo was conducted and has been presented in this communication. It is envisaged that similar in vitro embryogenesis studies involving plants belonging to different positions in phylogenetic tree would be immensely valuable in future research including in vitro embryogenesis.
... 2000, Ali vd. 2000, Milner 2001). Tüketimi prostat kanseri, kolorektal kanser, mide kanseri ve meme kanseri riskini azaltmaktadır (Dorant vd. ...
... triggering apoptosis in cancer cells. 25 Fukushima et al. (2001) attributed the anticancer effect of garlic to the orgonosulfur compounds in its content. In their study on TA100 Salmonella Typhimurium. ...
Garlic (Allium sativum) is a spice used for
centuries for both condiment and medicinal purposes.
Studies have shown that it has antibacterial, antiviral,
anti-inflammatory, antifungal, antimutagenic,
antioxidant, antiallergic, anti-aging, antitumoral and
immunostimulatory activities. Activation of caspase3 initiates the caspase activation chain, leading to
apoptosis. In this study aimed to determine the
apoptotic effect of DMSO-containing aged garlic
extracts (AGE) on Myoid Cancer Cell lines (HL-60).
Flow cytometry method and spectrophotometric
caspase-3 activity analyzes were used using human
lymphocyte cells as a control group. The highest
apoptotic effect on HL-60 cell lines was observed in
aged garlic extracts at a concentration of 12.5 mg/mL
(10.9%). It was determined that caspase-3 activity in
HL-60 cell lines increased by 1.28 to 3.02 times
compared to lymphocyte cells. It was concluded that
aged garlic extracts triggered apoptosis by increasing
the activity of caspase-3 in HL-60 cell lines. It is
thought that the aging of garlic has an anticancer
effect and additional studies on this subject may bring
new perspectives to cancer treatment.
... They have a high content of phytochemical compounds such as allyl methyl trisulfide and diallyl sulfide (Yahia 2017). These compounds inhibit proliferation and growth of cells, improve the immune system, modify the activation of cancerous substances, stimulate detoxifying enzymes and reduce the binding of the carcinogen-DNA (Milner 2001 ...
... They have a high content of phytochemical compounds such as allyl methyl trisulfide and diallyl sulfide (Yahia 2017). These compounds inhibit proliferation and growth of cells, improve the immune system, modify the activation of cancerous substances, stimulate detoxifying enzymes and reduce the binding of the carcinogen-DNA (Milner 2001 ...
Type 2 diabetes and obesity are factors that may cause elevation in the insulin level in the body, possibly leading to insulin resistance. Recent studies have shown the association between insulin resistance and obesity leading to various cancer types including breast, colon, liver, kidney, pancreatic, gastric, and leukemia. The increase in bioavailable insulin-like growth factor 1 (IGF-1) and hyperinsulinemia are instrumental in the formation of tumors in insulin-resistant patients. Overproduction of reactive oxygen species is another cause of developing cancer in insulin-resistant patients as it damages the DNA that contributes to mutagenesis and carcinogenesis. The adipose tissue in diabetic and obese individuals produces high levels of inflammation in cells which promotes tumorigenesis. Hence, weight loss and preventive diabetic therapies offer protective interventions in the development of cancers. In this chapter, we examined the interrelationship between obesity, diabetes, and the mechanism linking to cancer development and also the potential treatment recommendations that may help in controlling cancer.
... They have a high content of phytochemical compounds such as allyl methyl trisulfide and diallyl sulfide (Yahia 2017). These compounds inhibit proliferation and growth of cells, improve the immune system, modify the activation of cancerous substances, stimulate detoxifying enzymes and reduce the binding of the carcinogen-DNA (Milner 2001 ...
Phytochemicals are natural compounds in vegetables, fruits, and cereals. Eating enough quantities of whole grains, cultivated vegetables, and colorful fruits help in reducing the risk of certain cancers, as well as diabetes, overweight, high blood pressure, and heart disease. They can act as an antioxidant, nutritive protective or anti-inflammatory agents. Consuming a variety of vegetables, fruits, grains every day is the best way to get benefits from phytochemicals and antioxidants. There is still a considerable need for research on the importance and possible action mechanisms of phytochemicals against severe chronic diseases. This chapter sheds light on the prospective health impacts of eating fruits and vegetables on various diseases, and the health and nutritional effects of certain fruits and vegetables.
... They have a high content of phytochemical compounds such as allyl methyl trisulfide and diallyl sulfide (Yahia 2017). These compounds inhibit proliferation and growth of cells, improve the immune system, modify the activation of cancerous substances, stimulate detoxifying enzymes and reduce the binding of the carcinogen-DNA (Milner 2001 ...
Obesity is characterized by excessive accumulation of fats in the adipose tissues. Accumulation of excess fat releases a large number of adipokines that can cause obesity and diabetes mellitus due to irregularity between demand and the production of insulin. Obesity affects many organs and influences the heart, liver, intestines, respiratory organs, endocrine, and reproductive functions. Polydipsia, polyuria, weight reduction, coronary illness, kidney injury, diabetic foot, and diabetic ketoacidosis are pathophysiological manifestations and complications of diabetes. Obesity and overweight also contribute to the immune system dysfunction due to increased secretion of pro-inflammatory cytokines which are also risk factors for many types of cancer.
... They have a high content of phytochemical compounds such as allyl methyl trisulfide and diallyl sulfide (Yahia 2017). These compounds inhibit proliferation and growth of cells, improve the immune system, modify the activation of cancerous substances, stimulate detoxifying enzymes and reduce the binding of the carcinogen-DNA (Milner 2001 ...
Obesity and cancer are two of the major highly prevailing health disorders of public health concern. Obesity is a documented strong risk factor for many cancers particularly breast and pancreatic cancers. With a progressively increasing prevalence over the past few decades, obesity and cancer continues to leave a footprint of significant morbidity and mortality across different age groups and populations around the world. The global burden of obesity and cancer on health systems has reached alarming proportions necessitating ongoing research into novel approaches and innovative solutions for prevention and control. Such innovative research endeavors have yielded an evolution of efficacious drug treatments for obesity and cancers over time, some of which are used separately or in combination. This chapter highlights the meeting point between obesity and cancer with focus on their management.
... Allium savitum ( garlic) is used as a food, herbal medicine and has an excellent effect on different diseases such as cardiovascular diseases, cancer, some infection (Banerjee & Maulik, 2002;Bolton, Null, & Troetel, 1982;Fenwick, Hanley, & Whitaker, 1985;Graham, Anderson, & Lang, 1999;Milner, 2001). antibacterial and antiviral activity of this effective medicine also has been proved on influenza B and HSV (Yarnell, 2018). ...
Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.
... Traditionally, it has been used in reducing cholesterol, blood pressure, free radicle scavenger, anti-platelet activity, thromboxane inhibiting activity and cardioprotective [43] . Pharmacologically reported activities are antimicrobial, antioxidant [44] , antihypertensive [45] , cardioprotective [46] , anti-atherosclerotic [47] , antidiabetic [48] , cancer chemopreventive [49] , neuroprotective [50] , nephroprotective [51] and immunomodulatory [52] . Potentially active phytochemical constituents in this plant are alliin, allicin, allinase, ajoene, peroxidase, arginine, selenium, germanium and tellurium [43] . ...
... Still, some studies of colon and breast cancer did not find an association between diets high in glycemic load/ sugar and cancer [44,45]. There are many other dietary components imparting minor or misleading effect on cancer such as calcium, dairy products etc. [46]. ...
... Allyl sulfur compounds from garlic are effective against carcinogenesis by inhibiting the activation of carcinogens, modulating carcinogen metabolism, and inhibiting formation of DNA adducts with carcinogens, among other mechanisms. 33 Alcohol produces harmful effects in the stomach, causing direct damage to DNA 14 and inflammation. 34 Although our study failed to find significant associations between alcohol intake and GC risk, alcohol intake may modify the effect of garlic supplementation, with the protective effect of garlic supplementation on GC mortality seen particularly among those who did not drink alcohol. ...
Importance
The associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown.
Objective
To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors.
Design, Setting, and Participants
This is a secondary analysis of the Shandong Intervention Trial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019.
Interventions
Participants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo.
Main Outcomes and Measures
The primary outcomes were GC incidence and GC mortality (1995-2017). We also examined the progression of gastric lesions (1995-2003) as a secondary outcome.
Results
Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality (hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found.
Conclusions and Relevance
In this secondary analysis of a randomized clinical trial, smoking was associated with an increased risk of GC incidence and mortality. Not drinking alcohol was associated with a stronger beneficial effect of garlic supplementation on GC prevention. Our findings provide new insights into lifestyle intervention for GC prevention, suggesting that mass GC prevention strategies may need to be tailored to specific population subgroups to maximize the potential beneficial effect.
Trial Registration
ClinicalTrials.gov Identifier: NCT00339768
... Garlic (Allium sativum L.) is one of the important horticultural commodities and used daily as spices in Indonesian culinary because of its ability to improve the taste of food. Besides, garlic can be used as medicine since its biological activities that include antitumor and anticancer [1] ; [2] ; [3], cholesterollowering [4] and able to inhibit fungi and bacterial growth [5]. ...
The research was done at the Tissue Culture Laboratory of Center for Application of Isotope and Radiation Technology, Jakarta. Callus derived from shoot tip of garlic cloves was exposed to gamma rays, then cut into sized of 1 mm ³ and cultured in Gamborg medium enriched with plant growth regulators (PGRs) depends on the treatment. The PGRs applied are. The experiment was arranged in a randomized factorial design with 2 factors and 3 replications. The first factor was the doses of gamma rays (0, 10 and 20 Gy) and the second factor was different concentrations of PGRs (untreated, 1 and 2 ppm of thidiazuron (TDZ) and Zeatin). The result indicated that the application of 2 ppm TDZ or Zeatin promoted development on irradiated callus at the dose 10 Gy. The highest number of the shoot and the longest shoot were obtained from non-irradiated callus grown on medium enriched with 2 ppm TDZ, followed by 1 and 2 ppm Zeatin, 1 ppm TDZ and without PGRs. Irradiated callus at the dose 10 Gy grown on medium with 2 ppm TDZ was able to form a shoot, while other irradiated callusat the dose 29 Gy were not able to form the shoot.
... Garlic (Allium sativum) is one of these natural products that has been investigated for therapeutic approaches. Its medicinal uses, especially the anticarcinogenic potential, have been reviewed by Rivlin [10] and Milner [11]. ...
The purpose of this review is to discuss the molecular mechanisms underlying the anticancer properties of S-allylcysteine (SAC). Over the decades, evidence derived from in vitro and in vivo studies has shown that this predominant organosulfur component of aged garlic extract has multiple anticancer properties; hence, some potential mechanisms responsible for the anticarcinogenic action have been suggested. These mechanisms include induction of carcinogen detoxification, inhibition of cell proliferation and growth, mediation of cell cycle arrest, induction of cell death, inhibition of epithelial-mesenchymal transition and cell invasion, suppression of metastasis, and induction of immunomodulation in cancer cells. However, the actions and mechanisms are not comprehensive, and important aspects of the anticancer activities of SAC still need to be explored. In light of the current evidence, more specific studies, specifically clinical and epidemiological, are required to advance the promising use of SAC as a chemopreventive and therapeutic agent in cancer.
... Its leaf is thin and filet in dark green, and its flowers are small and pink like an umbrella at end of the stem. Allium sativum have been reported to be safe upon acute and sub-acute administration [29] and organosulfuric compounds has been found to reduce the risk of cancer in breast, larynx, colon, skin, womb, gullet, bladder, and lungs [30]. One of the most important Allium sativum compound, that is, Allicin, plays an important role in antitumor characteristics on breast and prostate cancer. ...
... Allicin is synthesized from glutathione via a number of intermediate compounds (Flow chart 8). It has been reported that Allium sativum and organosulfur compounds reduce the risk of cancer in breast, larynx, colon, skin, womb, gullet, bladder, and lung [71,72]. Moreover, allicin has been found to have antitumor effects on breast and prostate cancer by inducing apoptosis (Fig. 8) [73,74]. ...
Cancer is the second leading cause of death and morbidity in the world among the non-communicable diseases after cardiovascular ailments. With the advancement in science and research, a number of therapies have been developed to treat cancer including, chemotherapy, radiotherapy and immunotherapy. The chemo and radiotherapy have been in use since last two decades but these are not devoid of their own intrinsic problems such as myelotoxicity, cardiotoxicity, nephrotoxicity, neurotoxicity and immunosuppression. Hence there is an urgent need to develop alternative methods for treatment of cancer. Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. In this review we will introduce and discuss fifteen medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plant’s anticancer effect. Several phenolic and alkaloid compounds have been demonstrated to have anticancer effects on various types of cancers. The most fundamental and efficient role exhibited by these secondary plant metabolites against cancer involves removing free radicals and antioxidant effects, induction of apoptosis, cell cycle arrest and inhibition of angiogenesis. Moreover, recent studies have shown that plants and their metabolites may provide an alternative to the existing approaches including chemotherapies and radiotherapies in the treatment of cancer. In this review paper we will give a brief overview of important secondary metabolites having anticancer activity along with the molecular mechanisms involved against the disease at large. In addition to this we will explore the recent advances in secondary metabolites from various medicinal planst in prevention and treatment of cancer.
... There are numerous substances, known from traditional medicine, that are currently reinvestigated for their healing properties. The active compounds of garlic can prevent the development of cancer (chemo prevention) (Fleischauer & Arab, 2001;Lau, Tadi, & Tosk, 1990;Milner, 2001), enhance anti-cancer immunity (Lau, Tadi, & Tosk, 1990) and beneficially influence an ongoing chemotherapy, by minimizing its side effects (Li, Ito, Sumi, Fuwa, & Horie., 2009;Piasek, Bartoszek, & Namieśnik, 2009), together with grapes, tomato, spinach and beet root (Piasek, Bartoszek, & Namieśnik, 2009). The garlic molecules were found to prevent stomach (Lau, Tadi, & Tosk, 1990;Fleischauer & Arab, 2001) and colorectal cancers (Fleischauer & Arab, 2001) ─ through killing colon cancer cells (Ban et al., 2007;Bat-Chen, Golan, Peri, Ludmer, & Schwartz, 2010) ─ and to cure leukemia, through inhibiting the growth of human leukemia cell lines (Siegers, Steffen, Röbke, & Pentz, 1999) Utiger (2013) points out that Adam and Eve were vegetarians before their fall from the state of grace and considers that humanity will return to a vegetarian lifestyle on the resurrected Earth. ...
This treatise presents and combines theories and philosophies on the spiritual rebirthing and ascension process emanating from psychology, comparative mythology, and comparative religion. It addresses various states of the soul encountered on the mystical journey to Divine Union and the various ways God assists human beings in completing this process, both personally and collectively. The analysis of the soul regeneration process—the science of the saints—addresses human sanctification during earthly existence and eventually beyond if the worldly life does not suffice to complete this process. Furthermore, the role of the Divine Feminine in salvation history is highlighted as well as the importance of the alchemical communion between divine counterparts in the inauguration of the Millennium of Peace leading toward the New Jerusalem.
Cancer is one of the leading causes of death, despite advancements in health technologies and therapies. While effective, the treatment, chemotherapy can come with huge side effects. This review explores the diverse world of medicinal plants as potential cancer fighters. Numerous plant extracts have shown impressive anti-cancer properties in laboratory settings, offering a natural approach with potentially fewer side effects. However, further research is crucial to evaluate their efficacy and safety in human patients. This review will study the various medicinal plants and the chemical compounds that are promising as anticancer agents and will outline their potential mechanism of action.
Objective
This review aims to evaluate the latest techniques used in formulating epigallocatechin gallate (EGCG), analyse the difficulties encountered in the process, and offer perspectives on potential future advancements in epigallocatechin gallate formulations for both nutraceutical and pharmaceutical applications.
Methods
This work provides a thorough literature review, examines current epigallocatechin gallate formulation strategies, assesses solubility improvement approaches, examines obstacles, and summarises results regarding benefits and drawbacks. In nutraceuticals and pharmaceuticals, it identifies knowledge gaps and suggests future research avenues.
Results
This comprehensive review presents a synthesis of pivotal discoveries about epigallocatechin gallate formulations, particularly emphasising notable progress in enhancing solubility and the concomitant obstacles encountered in this pursuit. This review weighs the benefits and drawbacks, shedding light on areas that need further investigation in the pharmaceutical and nutraceutical fields.
Conclusion
This review synthesises current research on formulations containing epigallocatechin gallate, focusing on their various applications and the obstacles accompanying their implementation. Despite facing various challenges, the methodologies that have been investigated demonstrate potential. The comprehensive evaluation of both strengths and limitations highlights the imperative nature of continuous research. The conclusion provides opportunities for research in pharmaceuticals and nutraceuticals, outlining future directions.
Essential oils are the mixture of volatile ingredients and have been utilized extensively since antiquity. Regarding its bioactivity as an antibacterial, antiviral, antioxidant, and antidiabetic, the major significance and mode of action of these naturally occurring compounds are reviewed. Further, its crucial role in the suppression of cancer and chemoprevention is also emphasized. The traditional extraction methods such as steam distillation, hydrodistillation, hydro diffusion, and solvent extraction, and advanced (non-conventional) extraction methods such as solvent-free microwave extraction, subcritical extraction liquid, and supercritical fluid extraction have been discussed. Modern extraction techniques are thought to have the most potential because they require less time to extract, use less energy and less solvent, and emit less carbon dioxide. The chemical profile of essential oils has been explored in relation to several modern characterization approaches.
The biological properties (antioxidant and antimicrobial activity) of garlic during the transformation of raw garlic to black garlic using thermal treatment are discussed in this article, along with current research on bioactive compounds (organosulfur compounds, total phenolics, total flavonoids, etc.) and Maillard reaction-based products of garlic. Present-day treatments for garlic use a variety of technologies. These technologies employ various guiding principles to treat garlic and turn it into black garlic. High temperatures are used in thermal treatment technologies to treat garlic. The purpose of this review is to provide details on the effects of thermal processing on Maillard reaction-based products, such as hydroxymethyl furfural, Melanoidin, and polyphenols, and their capacity to preserve food. Black garlic is produced using various technologies, but thermal treatments are becoming more and more common because they are less expensive than other technologies. The study of the effects of thermal treatment techniques on Maillard reaction-based products like hydroxymethyl furfural, Melanoidin, sugars, polyphenols, and so forth, as well as interactions between garlic components and between nutrients and microbes, requires deeper investigations to fill knowledge gaps. The potential of thermal technologies for enhancing the bioactive compounds and Maillard reaction-based garlic products has been highlighted in this review. These compounds have the ability to inactivate spores and enliven microbe cells in garlic.KeywordsRaw garlicBlack garlicBioactive compoundsMaillard reactionThermal treatmentHMFMelanoidin
Objective:
Treatment of pulmonary fibrosis caused by paraquat (PQ) poisoning remains problematic. Amitriptyline (AMT) has multiple pharmacological effects. Here we investigated the anti-fibrotic effect of AMT on PQ-induced pulmonary fibrosis and its possible mechanism.
Methods:
C57BL/6 mice were randomly divided into control, PQ, PQ + AMT and AMT groups. Histopathology of the lungs, blood gas analysis, and levels of hydroxyproline (HYP), transforming growth factor β1 (TGF-β1) and interleukin 17 (IL-17) were measured. The siRNA transfection inhibited caveolin-1 in A549 cells, which induced epithelial-mesenchymal transition (EMT) by PQ and followed intervention with AMT. E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA) and caveolin-1 were studied by immunohistochemistry and western blot analysis. The apoptosis rate was measured by flow cytometry.
Results:
Compared with the PQ group, the PQ + AMT group displayed mild pathological changes in pulmonary fibrosis, lower HYP, IL-17 and TGF- β1 levels in lung, but high TGF- β1 in serum. Levels of N-cadherin and α-SMA in the lungs were significantly decreased, but caveolin-1 was increased, while SaO2 and PaO2 levels were higher. Compared with the PQ group, the apoptosis rate, N-cadherin and α-SMA levels in A549 cells were significantly decreased after PQ treatment and high dose AMT intervention (p < 0.01). The expressions of E-cadherin, N-cadherin and α-SMA in the PQ-induced cells transfected with caveolin-1 siRNA or siControl RNA were significantly different (p < 0.01), but the apoptosis rate was unaltered.
Conclusion:
AMT inhibited PQ-induced EMT in A549 cells and improved lung histopathology and oxygenation in mice by up-regulating caveolin-1.
This paper presents the phytochemical and antioxidant activities of single bulb garlic (Allium sativum) callus. The addition of sucrose by in vitro method can affect the secondary metabolites content of the callus. The experiment was designed to investigate the potential antioxidant activities of single bulb garlic callus with sucrose addition (30, 60, 90, and 120 g). The antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method; callus wet weight was analyzed using analysis of variance (ANOVA) followed by a Tukey test. The best callus, with an addition of 90 gL⁻¹ of sucrose into Murashige Skoog medium with a callus wet weight of 5.29 g, produced a yellowish-white callus color and crumb texture. Phytochemical analysis revealed that the callus of a single bulb of garlic contained secondary metabolic chemicals such as phenolics, alkaloids, saponins, and triterpenoids. The treatment with 90 gL⁻¹ of sucrose had the highest total phenolic content and antioxidant activity, with a TPC of 31.41 0.162 mg GAE/g and an IC50 of 33.78 g mL⁻¹. Single bulb garlic callus has the potential to be developed into an antioxidant agent.
Ethnopharmacological relevance:
Ayurvedic practitioners and herbal healers in India and China have extensively used garlic (Allium sativum L.) to treat cancers. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are major volatile organosulfur phytochemical constituents found in garlic.
Aim of the study:
To find new insight into the drug sensitizing effect of DADS and DATS on paclitaxel (PTX)-resistant triple-negative breast cancer cells (TNBC/PR).
Materials and methods:
This study estimates the non-toxic concentration of DADS and DATS against normal healthy breast epithelial cell line (MCF-12A) by using a trypan blue viability assay. Also, it evaluates the effect of DADS and DATS on the sensitization of established stable TNBC/PR cell clones (MDA-MB 231PR and MDA-MB 468PR) by MTT, BrdU incorporation, intracellular ROS, cell cycle, and apoptosis assays.
Results:
The results show that DADS and DATS are non-cytotoxicity against MCF-12A cells. Nevertheless, DADS and DATS have shown significantly high cytotoxicity against MDA-MB 231PR and MDA-MB 468PR cells. They also inhibited PTX-resistant cell proliferation by blocking the cell cycle. Further, they induced apoptosis by activation of caspase 3 and 9. N-acetyl cysteine pre-treatment inhibited DADS and DATS-induced intracellular ROS release. In silico study shows that DADS and DATS interact with a large extracellular loop (LEL) of CD151 with a binding energy of -4.0Kcal/mole and transmembrane domain (TM) with a binding affinity of 11.7 and 13.6Kcal/mole, respectively. They also inhibited the surface expression of CD151 in TNBC/PR cells.
Conclusion:
This study implies that DADS and DATS could be considered for sensitizing drug-resistant breast cancers.
Cancer is the second leading cause of death worldwide. The alternative natural therapies are required as they considered to have less toxic side effects compared to current chemotherapy. In the current review Web Science, PubMed, Scopus and Science Direct, were searched to provide information about medicinal plants that have shown anticancer activity against various forms of cancer.
Laurel (Laurus nobilis L.) is a strict endemic species of natural vegetation of the Mediterranean region, which is known for its medicinal, aromatic, forestry, ornamental and culinary properties. This species produces valuable essential oil (EO). The content of EO and its composition depend on different factors, e.g., genetic, cultural practices and environmental conditions. Among these, salt stress is a major limiting factor, which affects almost all plant functions. Similar to essential oils (EOs), biotic and abiotic stresses may stimulate or inhibit the emission of volatile compounds (VCs) in plant materials, suggesting that these substances can be responsible on stress defense strategies. Therefore, an experiment was conducted to assess the effect of different NaCl concentrations (0, 50, 100 and 150 mM) of the irrigation water on VCs of laurel leaves. Our results showed that salt stress affected the volatile metabolites compounds, mainly the major ones. For instance, 1,8-cineole and linalool were negatively affected by high salinity levels, while the opposite was observed for α-terpenyl acetate and methyl eugenol. The proportion of grouped compounds of laurel VCs also differed among the studied treatments. The relative content of oxygenated monoterpenes and monoterpene hydrocarbons, respectively the first and the second largest groups, decreased with increasing NaCl concentration. Differently, the relative amount of sesquiterpene hydrocarbon group increased, especially at 100 mM NaCl. These findings indicate that the cultivation of laurel in marginal lands, characterized by high salinity or low-quality water, must be carefully evaluated because it significantly varies the quality of its products.
Amaç: Kanser, hücrelerin kontrolsüz çoğalması sonucu ortaya çıkan ve her geçen yıl daha da yaygınlaşan hastalıkların başında gelir. Mevcut tedavi yöntemlerinin yetersizliği, seçici etkiye sahip ve nispeten daha az yan etkili yeni yöntem arayışı her geçen gün artmıştır. Son yıllarda kanser tedavi yöntemlerinden biri olarak yaygınlaşan fitoterapi, en dikkat çekici aday ve hızla gelişen bir alan oluşturmuştur. Bu çalışmada fitoterapi yönteminden yola çıkarak, pican cevizinin (Carya illinoinensis) yeşil-dış kabuğunun antikanser aktivitesi araştırılmıştır. Materyal ve Metod: Pican cevizi yeşil kabuğunun çeşitli kanser hücre hatları üzerindeki antikanser aktivitesi hücre kültürü yöntemi kullanılarak test edilmiştir. Bu kapsamda PC-3, DU-145, PNT1-A, HT-29, HCT-116 ve HUVEC hücre hatları, pikan cevizi yeşil-dış kabuğu hekzan ekstraktı ile tedavi edilerek sitotoksik değeri (MTT boyaması) belirlenmiştir. Belirlenen doz ve hücreler kullanılarak Annexin V/PI boyaması ile apoptotik hücre yüzdesi ve PI boyaması ile ise hücre döngüsü üzerine etkileri araştırılmıştır. Bulgular: Elde edilen deney sonuçlarına göre pican cevizi yeşil-dış kabuk hekzan ekstraktı seçici etki göstererek en yüksek sitotoksik etkiyi prostat kanseri hücre hattı olan PC-3 üzerine gösterdiği tespit edilmiştir (IC50: 40.32µg/ml). Belirlenen IC50’unda apoptotik hücre yüzdesi %94 ve G0/G1 fazında tutulan hücre miktarı ise %59.2 olduğu bulunmuştur. Sonuç: Bu çalışma sonucunda PC-3 hücrelerin, hücre bölünmesini yavaşlattığı ve hücrelerde apoptozisi tetiklediği tespit edildi. Bu sonuçlara göre, farmakolojik alanda pican cevizi yeşil-dış kabuğunun kanser tedavisinde kullanılabilecek alternatif bir bitki adayı olduğu ve bu alanda yapılacak çalışmalara yol gösterici olacağı öngörülmektedir.
Cancer is a prominent cause of mortality globally, and it becomes fatal and incurable if it is delayed in diagnosis. Chemotherapy is a type of treatment that is used to eliminate, diminish, or restrict tumor progression. Chemotherapeutic medicines are available in various formulations. Some tumors require just one type of chemotherapy medication, while others may require a combination of surgery and/or radiotherapy. Treatments might last from a few minutes to many hours to several days. Each medication has potential adverse effects associated with it. Researchers have recently become interested in the use of natural bioactive compounds in anticancer therapy. Some phytochemicals have effects on cellular processes and signaling pathways with potential antitumor properties. Beneficial anticancer effects of phytochemicals were observed in both in vivo and in vitro investigations. Encapsulating natural bioactive compounds in different drug delivery methods may improve their anticancer efficacy. Greater in vivo stability and bioavailability, as well as a reduction in undesirable effects and an enhancement in target-specific activity, will increase the effectiveness of bioactive compounds. This review work focuses on a novel drug delivery system that entraps natural bioactive substances. It also provides an idea of the bioavailability of phytochemicals, challenges and limitations of standard cancer therapy. It also encompasses recent patents on nanoparticle formulations containing a natural anti-cancer molecule.
Fruits and vegetables (FVs) have long been a major source of nutrients and dietary phytochemicals with outstanding physiological properties that are essential for protecting humans from chronic diseases. Moreover, the growing demand of consumers for nutritious and healthy foods is greatly promoting the increased intake of FVs. Allium (Alliaceae) is a perennial bulb plant genus of the Liliaceae family. They are customarily utilized as vegetable, medicinal, and ornamental plants and have an important role in agriculture, aquaculture, and the pharmaceutical industry. Allium plants produce abundant secondary metabolites, such as organosulfur compounds, flavonoids, phenols, saponins, alkaloids, and polysaccharides. Accordingly, Allium plants possess a variety of nutritional, biological, and health-promoting properties, including antimicrobial, antioxidant, antitumor, immunoregulatory, antidiabetic, and anti-inflammatory effects. This review aims to highlight the advances in the research on the bioactive components, physiological activities and clinical trials, toxicological assessment for safety, and applications of different Allium plants. It also aims to cover the direction of future research on the Allium genus. This review is expected to provide theoretical reference for the comprehensive development and utilization of Allium plants in the fields of functional foods, medicine, and cosmetics.
Bioactive compounds are usually described as molecules that can be found in small quantities in food and other natural matrixes that can represent an extra-nutritional contribution to the diet due to their related health effects. Membrane technology is an emerging method aimed at purifying different ingredients which has received considerable attention due to the low energy requirements in comparison to other concentration processes, wide range of applications, simplicity in continuous operation and easy integration. One of the main applications of this technique is the recovery and purification of food bioactive ingredients. Nature is an endless source of bioactive compounds that can be used for the formulation of new ingredients or other products. Therefore, it is essential to determine which are those main bioactive compounds present in food and their main properties to correctly apply this technique. The aim of this chapter is to revise those main bioactive compounds found in food, their occurrence, and main sources as well as their main properties. Furthermore, specific limitations for the application of membrane technology will be addressed whenever necessary.
Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor‐α36 (ER‐α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER‐α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl‐2 expression. However, the ER‐α36 expression knockdown attenuated DAS‐induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER‐α36‐mediated activation of the MAPK/ERK signaling induced by estrogen. Thus, our results indicate that ER‐α36 signaling is involved in DAS‐induced inhibition of HCC cell growth both in vitro and in vivo.
Wounds can occur due to any injury, disease state or insect bite or abrasions. Wound healing is a complex process that includes many phases and involves a number of inflammatory mediators wound can be classified as acute and chronic. Other than this wound can also be classified on the basis of layer of skin that gets damaged: Superficial wound, Partial thickness wound and Full thickness wound. Garlic (Allium sativum) has been used as food and also used for the treatment of many diseases, for healing of wounds etc. Garlic is perennial liliaceous herb with a bulb having organosulphur compounds like Diallyl disulphide, diallyl sulphide, diallyl trisulphide and sulphur dioxide others are allin, allicin, etc. Garlic having major properties includes anti-cancer, against cardiovascular disease, antioxidant,anti-microbial, in wound healing etc
Legitimate nutrition assumes a significant role in preventing diseases and, in this way, nutritional interventions establish vital strategies in the area of public health. Nutrigenomics centres on the different genes and diet in an individual and how an individual’s genes influence the reaction to bioactive foodstuff. It targets considering the genetic and epigenetic interactions with nutrients to lead to a phenotypic alteration and consequently to metabolism, differentiation, or even apoptosis. Nutrigenomics and lifestyle factors play a vital role in health management and represent an exceptional prospect for the improvement of personalized diets to the individual at risk of developing diseases like cancer. Concerning cancer as a multifactorial genetic ailment, several aspects need to be investigated and analysed. Various perspectives should be researched and examined regarding the development and prognosis of breast and colon cancer. Malignant growth occurrence is anticipated to upsurge in the impending days, and an effective anticipatory strategy is required. The effect of dietary components, basically studied by nutrigenomics, looks at gene expression and molecular mechanisms. It also interrelates bioactive compounds and nutrients because of different 'omics' innovations. Several preclinical investigations demonstrate the pertinent role of nutrigenomics in breast and colon cancer, and change of dietary propensities is conceivably a successful methodology for reducing cancer risk. The connection between the genomic profile of patients with breast or colon cancer and their supplement intake, it is conceivable to imagine an idea of personalized medicine, including nutrition and medicinal services.
In this study, antimutagenic effects of ethanolic extracts of Stachys thirkei and Stachys annua subsp. annua belonging to Lamiaceae family that grow in Duzce of Turkey were investigated on Salmonella typhimurium TA98 and TA100 strains without metabolic activation using Salmonella/microsome test system. Three different concentrations (0.025, 0.05 and 0.1 mg/plate) of the ethanolic extracts of S. thirkei and S. annua subsp. were used as active materials in which the major components were 2-ethylhexanol (30.012%) and 2-beta-pinene (26.40%), respectively. The highest concentration (0.1 mg/plate) of S. thirkei had a moderate antimutagenic effect on the Salmonella typhimurium TA98 strain with a 26.79% inhibition rate. It was also established that the extract of S. thirkei at highest concentration (0.1 mg/plate) exhibited strong antimutagenic effect (with 44.03% maximum inhibition) on TA100 strain. Furthermore, it was found that 0.05 mg/plate ethanolic extract showed moderate antimutagenic activity with 25.55% inhibition rate. The highest concentration (0.1 mg/plate) of ethanolic extract of S. annua subsp. showed moderate antimutagenic activity on both Salmonella typhimurium TA98 and TA100 strains with inhibition rates of 20.39 and 22.13%, respectively. No antimutagenic activity on Salmonella typhimurium TA98 and TA100 strains was observed at the lowest doses of both plant species. As a result, it is concluded that S. thirkei and annua subsp. have antimutagenic activity and further studies may be recommended in terms of different parameters.
Biological redox signaling plays an important role in many diseases. Redox signaling involves reductive and oxidative mechanisms. Oxidative stress occurs when reductive mechanism overwhelms oxidative challenges. Cellular oxidative stress occurs when reactive oxygen/nitrogen species (RO/NS) exceed the cellular reductive/antioxidant capacity. Endogenously produced RO/NS from mitochondrial metabolic citric-acid-cycle coupled with electron-transport-chain or exogenous stimuli trigger cellular signaling events leading to homeostatic response or pathological damage. Recent evidence suggests that RO/NS also modulate epigenetic machinery driving gene expression. RO/NS affect DNA methylation/demethylation, histone acetylation/deacetylation or histone methylation/demethylation. Many health beneficial phytochemicals possess redox capability that counteract RO/NS either by directly scavenging the radicals or via inductive mechanism of cellular defense antioxidant/reductive enzymes. Amazingly, these phytochemicals also possess epigenetic modifying ability. This review summarizes the latest advances on the interactions between redox signaling, mitochondrial metabolism, epigenetics and redox active phytochemicals and the future challenges of integrating these events in human health.
Healthy diet and proper nutrition are basic necessity of life and play a key role in preventing diseases. Nutrigenomics (NG) is an emerging approach in nutritional research which deals with the gene-diet interactions. The concept of nutrigenomics is not new and it is commonly associated with “inborn errors of metabolism”, the rare genetic (inherited) disorders in which the body cannot properly turn food into energy. These disorders are related to insufficient availability of metabolic enzymes or cofactors due to alteration of gene. Usually cure of these diseases lies in restricted diet. Presently non communicable diseases (NCDs) like cardiovascular diseases, obesity, diabetes and cancers are outnumbering the other health ailments among the different human populations of world. The main reason behind the occurrence of these NCDs is the abruptly changing life style and food habits after industrial revolution. With the advent of industrial revolution and economical concerns, the life style of people across the world has changed so much so that it resulted in approximately millions of death cases due to these NCDs. Study related to NG is one step forward in nutritional research involving the techniques of nutrition, molecular biology, genomics, bioinformatics, molecular medicine and epidemiology together to understand the role of food as an epigenetic factor which unravel its role in the occurrence of these diseases. Hence, under the prevailing scenario of world health, it has become an urgency to boost NG research to find cure for dreaded diseases caused due to lack of healthy food and improper nutrition. Thus, such type of research findings ensures the effective benefit of genomic revolution for mankind near future.
Nutrigenomics, the junction between health, diet, and genomics, can be viewed as the blend of molecular nutrition and genomics. Nutrigenomics will provide a far better understanding of how nutrition affects metabolic pathways and homeostatic regulation, how this regulation is disrupted in the early stages of diet-related disease, and the extent to which individual sensitizing genotypes lead to such diseases. Ultimately, nutrigenomics will certainly lead to evidence-based nutritional intervention approaches for preventing diet-related disease.
The medicinal uses of garlic (Allium sativum) and its constituents have been known for centuries, though its mode of action is still undetermined. Several epidemiological and laboratory studies indicate a potential anti-carcinogenic effect of garlic and some of its constituents. In this study we investigated the effect of aged garlic extract (AGE) and two of its components, S-allylcysteine (SAC), and S-allyl-mercaptocysteine (SAMC) on human breast cancer cells, MCF-7 and MCF-7(ras). Transfection of v-H-ras in MCF-7 cells gives rise to a highly aggressive subset of cells that is estrogen independent and has a five fold greater colony forming efficiency in soft agar than the parent cell line. The modulatory effect of AGE, SAC and SAMC on growth and glutathione cycle was examined in the two cell lines. We noted an anti-proliferative response to SAC and SAMC on both anchorage dependent and independent conditions and an alteration in glutathione level without significant concurrent changes in the glutathione metabolizing enzymes.
The lipoxygenase catalyzed epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was examined. Epoxidation of the BP-7,8-diol was catalyzed by 5- and 15-lipoxygenase in the presence of either arachidonic acid, gamma-linolenic acid, or 15-hydroperoxyeicosatetraenoic acid (15-HPETE). The anti-9,10-epoxy-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene isomer was formed in greater quantities than the syn isomer, indicative of peroxyl radical mediated epoxidation. Epoxidation was dependent on time, enzyme and fatty acid concentration. There was no difference in the time course of epoxidation with either arachidonic acid or 15-HPETE, although the initial rate of oxygen consumption was approximately 55-fold greater with arachidonic acid. The lipoxygenase inhibitor and anti-oxidant nordihydroguaiaretic acid inhibited epoxidation in a dose-dependent manner in incubations initiated with either arachidonic acid or 15-HPETE. The anti-oxidant butylated hydroxyanisole also inhibited the epoxidation. Incubations conducted under anaerobic conditions with 15-lipoxygenase and either arachidonic acid or 15-HPETE significantly decreased epoxidation. This suggests that the oxygen inserted into BP-7,8-diol is derived from the atmosphere. The epoxidizing peroxyl radicals could not be detected but their precursors, carbon-centered radicals, were detected by using the ESR spin trapping technique in incubations of 15-lipoxygenase with 15-HPETE. This radical, formed by reduction and rearrangement of the hydroperoxide, may trap oxygen to form a peroxyl radical. We propose that the epoxidizing species is a peroxyl radical derived from 15-HPETE rather than from arachidonic acid. This proposal is based on the similar amounts of epoxidation, but dissimilar amount of oxygen consumed with both fatty acids. Since lipoxygenases are widely distributed in vivo, especially in areas where tumors arise such as the pulmonary epithelium, peroxyl radical formation by these enzymes may have an important role in chemical carcinogenesis.
Previous work has shown that the efficacy of cancer prevention by selenium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium. Additionally, supplementation of Se-garlic inhibited the post-initiation phase of mammary carcinogenesis when it was given continuously to the animals. In this report, experiments were carried out in which treatment with the Se-garlic was started after carcinogen dosing (DMBA or MNU) but was restricted to either the early or late stage of neoplastic progression. The results from these two models showed that a short-term exposure to the Se-garlic for 1 month immediately following carcinogen administration was just as effective in cancer prevention as the continuous exposure regimen (5 months), suggesting that the Se-garlic may irreversibly alter the process of clonal expansion and/or selection of transformed cells during their early stage of development. Plasma and mammary tissue selenium levels essentially returned to basal levels at 1 month after withdrawal of supplementation. These observations imply that the outcome of cancer protection by short-term Se-garlic intervention was not due to a slow turnover, and therefore a lingering presence, of selenium in the target organ or in the circulation. The above finding was in contrast to that of a second study in which Se-garlic was supplemented starting at 13 weeks after carcinogen treatment. With this protocol, the number of new tumors and the number of new tumor-bearing rats found during the intervention period (weeks 13 to 22) were not statistically different between the control and supplemented groups, suggesting that Se-garlic had a minimal effect on the later stages of mammary carcinogenesis.
The involvement of cyclooxygenase in DMBA metabolism and DNA adduct formation was examined in vitro using incubations of purified ovine prostaglandin H synthase-1 (PHS-1 ; 400 units) or isolated rat mammary microsomes (200 ug), DMBA-3,4-dihydrodiol (50 uM) calf-thymus DNA (Img/mL) and arachidonic acid (100 uM). Indomethacin (100 uM) inhibited the occurrence of DNA adducts by greater than 95% when catalyzed by either purified PHS-1 or mammary microsomes. Indomethacin feeding also blocked the in vivo occurrence of DMBA metabolites bound to mammary epithelial cell DNA of female Sprague-Dawley rats (55 d old). In rats fed a 5% corn oil diet for 2 wks, the total quantity of DMBA metabolites bound to DNA was 81 nmol adduct/mol DNA compared to 173 nmol adduct/mol DNA in those fed the 20% corn oil diet (P<0.05). Indomethacin supplementation (150 umol/kg diet) inhibited total DNA adducts by 65 and 76%, respectively, in rats fed a 5 or 20% corn oil diet Although both ami- and syn-diolepoxide-DNA adducts were inhibited by indomethacin, decreased anti-deoxyguanosine adducts accounted for the greatest reduction in adducts. These studies demonstrate that cyclooxygenase participates in the bioactivation of DMBA and high dietary corn oil increases the initiation of DMBA carcinogenesis at least in part via influencing this enzyme.
The present studies assessed the impact of various sources of garlic and their constituents (water- and ethanol-extracts and
S-allylcysteine) on the in vivo binding of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) to rat mammary cell DNA. The provision of dietary raw garlic
powder (2%) or its water-extract (1.5%) reduced DMBA-DNA binding by 33 and 46% respectively. Dietary supplementation with
a commercially available deodorized garlic powder (powder A) at 2 or 4% depressed the occurrence of adducts by 50 and 78%
respectively, while providing a commercially available high sulfur garlic preparation (powder B) at 2% reduced binding by
56%. A pair-feeding study revealed that the depression in carcinogen binding was independent of food intake or weight gain.
Although 1% raw garlic powder did not significantly influence the occurrence of DMBA-DNA adducts, an equivalent as the water-extract
(0.75%), the ethanol-extract (0.015%) or commercially available powders (A and B) reduced DMBA adducts in mammary tissue by
44, 25, 71 and 65% respectively. Dietary fortification with S-allylcysteine (SAC), a water-soluble constituent of processed garlic, caused a progressive decrease in the binding of DMBA
to DNA. Studies with SAC suggest the primary effect of garlic and its constituents is on the bioactivation and binding of
the carcinogen rather than DNA repair. These data reveal that several forms of garlic are effective, although variable, in
altering carcinogen bioactivation and presumably chemically induced carcinogenesis.
Precision-cut liver slices from phenobarbital-induced rats were incubated for 6 h with the model hepatotoxin bromobenzene (BB) at a final concentration of 1 mM. Severe toxicity was indicated by a decreased K+, adenosine triphosphate and glutathione (GSH) content of the slices, increased release of alanine aminotransferase and lactate dehydrogenase into the medium, and increased formation of thiobarbituric acid reacting substances. Pretreatment of animals for 7 days with aged garlic extract (AGE) (Kyolic®) at doses of 2 and 10 ml/kg/day dramatically reduced the toxicity of BB in a dose-dependent manner. The GSH content of liver slices from rats treated with AGE at 2 or 10 ml/kg/day increased by 50 and 80%, respectively. The BB-induced decrease in GSH content was less in slices derived from AGE-treated rats compared with slices from control rats. Pretreatment with AGE did not affect cytochrome P450 when assayed as 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities in hepatic microsomes. Thus, the mechanism by which pretreatment with AGE protects against BB hepatotoxicity involves both an elevation of hepatic GSH content, and a GSH sparing effect, possibly due to conjugation of organosulphur compounds in AGE with toxic BB metabolites. Only this GSH sparing effect was seen in our earlier study on the in vitro hepatoprotective effect of AGE [Wang et al., 1998. Toxicology 126, 213–222].
This study was undertaken to elucidate the mechanism of organ specificity and differential efficacy of garlic organosulfides (OSCs) [diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS)] in preventing benzo(a)pyrene (BP)-induced tumorigenesis in mice. The results of the present study reveal a good correlation between chemopreventive efficacies of garlic OSCs and their inductive effects on the expression of NAD(P)H:quinone oxidoreductase (NQO), an enzyme implicated in the detoxification of activated quinone metabolites of BP. Treatment of mice with DADS and DATS, which are potent inhibitors of BP-induced forestomach tumorigenesis, resulted in a statistically significant increase (2.4- and 1.5-fold, respectively) in forestomach NQO activity. In addition, DADS and DATS were much more potent inducers of forestomach NQO activity than DAS, which is a weak inhibitor of BP-induced forestomach tumorigenesis than the former compounds. Propyl-group containing OSCs (DPS and DPDS), which do not inhibit BP-induced tumorigenesis, did not affect forestomach NQO activity. Similar to forestomach, a good correlation was also observed between effects of these OSCs against BP-induced pulmonary tumorigenesis and their effects on NQO expression in the lung. For example, treatment of mice with DAS, which is a potent inhibitor of BP-induced pulmonary tumorigenesis, resulted in about 3.2-fold increase in pulmonary NQO activity. On the other hand, this activity was increased by about 1.5-fold upon DATS administration, which does not inhibit BP-induced cancer of the lung. In conclusion, our results suggest that induction of NQO may be important in anti-cancer effects of garlic OSCs.
Diallyl disulfide caused growth inhibition and differentiation of DS19 mouse erythroleukemic cells as judged by hemoglobin synthesis and induction of acetylcholinesterase activity. There was a 50% inhibition of cell division at about 0.25 mM diallyl disulfide which was much more effective than diallyl sulfide. K562 human erythroleukemia cells and mouse melanoma cells were more resistant to the action of diallyl disulfide. Thymidine incorporation into DNA in 7800NJ and 7288CTC rat hepatoma cells and in T47D and MCF7 human breast cancer cells was inhibited by 1-2 mM diallyl disulfide. Administration of diallyl disulfide to rats bearing Morris hepatomas caused marked inhibitory effects on precursor incorporation into DNA and protein in both hepatomas and in livers after a dose of 400 mg/kg body weight, but only small differences were seen at a less toxic dose of 200 mg/kg.
A variety of compounds derived from garlic bulbs have been shown in animal systems to possess anticancer properties. However, little information is available regarding the effectiveness of garlic in the prevention or treatment of human cancers. In the current study, we have assessed the ability of S-allyl cysteine (SAC), a derivative of aged garlic extract, to affect the proliferation and differentiation of LA-N-5 human neuroblastoma cells in vitro. Time-and dose-dependent inhibition of cell grow was observed in cultures treated with SAC for at least 2 days, with a half-maximal response at approximately 600 micrograms/ml. SAC treatment was unable to induce differentiation in neuroblastoma cells as assessed by morphological, biochemical and molecular markers. In addition, SAC was unable to potentiate the effects of retinoic acid and 8-bromo-cyclic AMP, agents known to promote differentiation of LA-N-5 cells. Our results indicate that SAC can inhibit human neuroblastoma cell growth in vitro. However, the apparent inability of this compound to induce differentiation may limit its therapeutic potential.
The present studies determined the influence of dietary supplements of garlic powder (0, 1, 2 or 4%) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors and on the in vivo occurrence of mammary DMBA-DNA adducts in rats. Diets were offered 2 weeks before and 2 weeks following DMBA treatment (25 mg/kg body wt). An additional group was fed the 2% garlic powder diet throughout the 20 week study. Although food intake and weight gain were not influenced, dietary garlic powder supplementation did significantly delay the onset of first tumors (P < 0.01) and did reduce the final mammary tumor incidence (P < 0.01). Consumption of garlic powder also significantly depressed the in vivo binding of DMBA to mammary cell DNA. Binding of both anti- and syn-dihydrodiol epoxides to DNA was depressed in rats fed supplemental garlic powder. The activity of glutathione S-transferase (GST) in mammary and liver tissue from rats fed 2% dietary garlic powder was higher than observed in tissues from rats fed the basal diet. No further increase in GST activity occurred when the dietary garlic content was increased from 2 to 4%. Final mammary tumor incidence was found to correlate positively with total DMBA-DNA binding and the quantities of individual DMBA-DNA adducts. The present studies demonstrate that garlic powder is effective in inhibiting DMBA-induced mammary tumors, possibly by reducing DMBA-DNA binding.
The anticarcinogenic activities of regular (soil-grown) garlic and selenium-enriched garlic (cultivated in the greenhouse) were evaluated using the 7,12-dimethylbenz[a]anthracene-(DMBA) induced mammary tumor model in rats. In Experiment 1, milled regular garlic powder was added to the basal AIN-76A diet at 20 g/kg. The results from different schedules of supplementation suggested that a continuous treatment, which started before DMBA and persisted for the entire duration of the study, was most effective in tumor suppression. In Experiment 2, selected allyl group-containing sulfides that are normal constituents of garlic extract were given by gavage in three single doses immediately before DMBA. Several structurally related compounds were found to be protective during the initiation phase in the mammary cancer model. Although the present study was not designed specifically to elucidate the structure-activity relationship with respect to sulfur chain length or alkyl versus alkenyl substitution, our data showed that diallyl disulfide was more active than diallyl sulfide or allyl methyl sulfide. In Experiment 3, the anticarcinogenic activity of selenium-enriched garlic (containing 150 ppm Se dry weight from growth in a selenium-fertilized medium) was compared with that of regular garlic as well as selenite. Animals given the selenium-enriched garlic (final concentration 3 ppm Se in the diet) developed the fewest mammary tumors. Tissue selenium levels, however, were lower in these animals than in those fed the same amount of selenium from selenite. Our study demonstrated the feasibility of achieving cancer prevention with the use of a selenium-rich food system.(ABSTRACT TRUNCATED AT 250 WORDS)
Diallyl sulfide (DAS), a major component of garlic oil, is an inhibitor of tumorigenesis by various metabolically activated carcinogens. In rats, pretreatment with DAS has been observed to suppress completely the induction of oesophageal neoplasms by N-nitrosomethylbenzylamine (NMBzA) (Wargovich et al. (1988) Cancer Res., 48, 6872-6875). This communication reports the effects of DAS on overall NMBzA metabolism and on DNA methylation of NMBzA in vivo under conditions equivalent to a single treatment of the chemoprevention assay. Male Fischer 344 rats received a single i.g. dose of DAS (200 mg/kg body wt) followed by an s.c. injection of [methyl-14C]NMBzA (3.5 mg/kg). In controls, exhalation of 14CO2 was complete within 5 h (t1/2max = 1.2 h), with 50% of the injected radioactivity recovered as 14CO2. When DAS was given 3 h prior to [methyl-14C]NMBzA, 49% of the injected radioactivity was released within 10 h (t1/2max = 3 h). When DAS was administered 18 h before the carcinogen, 42% of [methyl-14C]NMBzA was converted to 14CO2, with exhalation complete after 6 h (t1/2max = 1.8 h). We further examined the effects of acute doses of 10-200 mg/kg of DAS on DNA methylation by a single dose of NMBzA (3.5 mg/kg; survival time, 6 h) administered 3 h later. At 200 mg/kg, DAS inhibited the formation of O6-methyldeoxyguanosine (O6-MEdG) in oesophagus (-26%), nasal mucosa (-51%), trachea (-68%) and lung (-78%). In liver, levels of 7-MEdG were reduced by 43%. Decreases in DNA methylation were proportional to dose for > 25 mg/kg of DAS in oesophagus, liver and nasal mucosa, for 25-200 mg/kg in trachea and 10-50 mg/kg in lung. The dose-activity relationship for inhibition by DAS of DNA methylation by NMBzA suggests that short-term modulation of carcinogen bioactivation in situ contributes to but may not be sufficient for the chemo-prevention of nitrosamine tumorigenesis by DAS.
N-Nitroso compounds (NOCs) are known to be strong carcinogens in various animals including primates (Preussman and Stewart, (1984) N-Nitroso Compounds). Human exposure to these compounds can be by ingestion or inhalation of preformed NOCs or by endogenous nitrosation from naturally occurring precursors (Bartsch and Montesano, Carcinogenesis, 5 (1984) 1381-1393; Tannebaum (1979) Naturally Occuring Carcinogens, Mutagens and Modulators of Carcinogenesis; Shephard et al., Food Chem. Toxicol., 25 (1987) 91-108). Several factors present in the diet can modify levels of endogenously formed nitrosamines by acting as catalysts or inhibitors. Compounds in the human diet that alter nitrosamine formation would thus play an important role in carcinogenesis study. Earlier researchers have reported the nitrite scavenging nature of sulphydryl compounds (Williams, Chem. Soc. Rev., 15 (1983) 171-196). We therefore studied the modifying effect of sulphydryl compounds viz., cysteine (CE), cystine (CI), glutathione (GU), cysteamine (CEA), cystamine (CEI), cysteic acid (CIA) and thioglycolic acid (TGA) on the nitrosation of model amines viz., pyrrolidine (PYR), piperidine (NPIP) and morpholine (NMOR). Many of these compounds are present in the food we consume. The present work also describes the inhibitory effect of onion and garlic juices on the nitrosation reactions. Both onion and garlic are known to contain sulphur compounds (Block, Sci. Am., 252 (1985) 114-119). Most of these compounds behave as antinitrosating agents and their inhibitory activity towards formation of carcinogenic nitrosamines, under different conditions is described.
Diallyl sulfide (DAS), a component of garlic oil, has been shown to inhibit tumorigenesis by several chemical carcinogens. Our previous work demonstrated that DAS inhibited the metabolic activation of carcinogenic nitrosamines, including the tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in rat lung and nasal mucosa microsomes. In the present study, the effects of DAS on the tumorigenicity and the metabolism of NNK in A/J mouse lung were examined. Female A/J mice at 7 weeks of age were pretreated with DAS (200 mg/kg body wt in corn oil, p.o) daily for 3 days. Two hours after the final DAS treatment, the mice were either given a single dose of NNK (2 mg/mouse, i.p.) and kept for an additional 16 weeks for determining the production of pulmonary tumors, or were killed immediately so as to measure the microsomal activity in metabolizing NNK. In comparison to the vehicle control group, DAS pretreatment significantly decreased the incidence of NNK-induced lung tumors (37.9 versus 100%) and the tumor multiplicity (0.6 versus 7.2 tumors/mouse). In pulmonary metabolism of NNK, DAS pretreatment reduced the rates of formation of keto aldehyde, keto alcohol, NNAL-N-oxide, and NNK-N-oxide by 70-90%. In addition, the formation of NNK oxidative metabolites from NNK in the liver microsomes from DAS-pretreated mice was remarkably reduced. DAS also inhibited the metabolism of NNK in mouse lung microsomes in vitro. These results demonstrate that DAS is an effective chemopreventive agent against NNK-induced lung tumorigenesis, probably by inhibiting the metabolic activation of NNK.
Prostaglandin H synthase (PHS) catalyzes the oxidation of arachidonic acid to prostaglandin H2 in reactions which utilize two activities, a cyclooxygenase and a peroxidase. These enzymatic activities generate enzyme- and substrate-derived free radical intermediates which can oxidize xenobiotics to biologically reactive intermediates. As a consequence, in the presence of arachidonic acid or a peroxide source, PHS can bioactivate many chemical carcinogens to their ultimate mutagenic and carcinogenic forms. In general, PHS-dependent bioactivation is most important in extrahepatic tissues with low monooxygenase activity such as the urinary bladder, renal medulla, skin and lung. Mutagenicity assays are useful in the detection of compounds which are converted to genotoxic metabolites during PHS oxidation. In addition, the oxidation of xenobiotics by PHS often form metabolites or adducts to cellular macromolecules which are specific for peroxidase- or peroxyl radical-dependent reactions. These specific metabolites and/or adducts have served as biological markers of xenobiotic bioactivation by PHS in certain tissues. Evidence is presented which supports a role for PHS in the bioactivation of several polycyclic aromatic hydrocarbons and aromatic amines, two classes of carcinogens which induce extrahepatic neoplasia. It should be emphasized that the toxicities induced by PHS-dependent bioactivation of xenobiotics are not limited to carcinogenicity. Examples are given which demonstrate a role for PHS in pulmonary toxicity, teratogenicity, nephrotoxicity and myelotoxicity.
The sulfur-containing compound ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) which arises from alliin, a cysteine derivative stored in garlic bulbs, was produced synthetically by decomposition of allicin. Its cytotoxic effect was tested using human primary fibroblasts (FS4), a permanent, non-tumorgenic cell line derived from baby hamster kidney cells (BHK21) and a tumorgenic lymphoid cell line derived from a Burkitt lymphoma (BJA-B). The cytotoxic action was in the range 2-50 micrograms/ml depending on the cell density. ED50 values, estimated on the basis of fmol ajoene/cell, revealed slightly higher doses for the primary cell (FS4) than the permanent line (BHK), whereas the tumorgenic BJA-B cells were most sensitive.
The present paper reports the chemopreventive action of garlic on 3-methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin young adult Swiss albino mice. Insertion of sterile cotton thread impregnated with beeswax containing approximately 600 micrograms of MCA inside the canal of uterine cervix results in the appearance of precancerous and cancerous lesions in the cervical epithelium. In this experimental cervical carcinogenesis model system, if garlic was administered orally at the dose level of 400 mg/kg body wt./day for 2 weeks before and 4 weeks following carcinogen thread insertion. The cervical carcinoma incidence, as compared with that of the positive control (73%), was 23%. This decline in the incidence of carcinoma was highly significant (P less than 0.01). Hyperplastic and dysplastic changes did not show any definite correlation with the garlic treatment.
Organosulfur compounds (OSCs) present in garlic and onion oil have been shown to inhibit chemical carcinogenesis. In this study, we compared the chemopreventive efficacy of five lipid- and four water-soluble OSCs using the murine nuclear aberration assay. Administration of diallyl sulfide and S-allyl cysteine p.o. at a dose of 200 mg/kg 3 h prior to i.p. 1,2-dimethylhydrazine (DMH) injection (20 mg/kg) significantly inhibited colonic nuclear damage in female C57Bl/6J mice by 47% and 36%, respectively. The inhibitory effect of S-allyl cysteine was found to be dose dependent. The other OSCs did not affect the level of DMH-induced nuclear toxicity. Furthermore, the incidence and frequency of colonic tumors induced by DMH (20 mg/kg, 10 weekly i.p. injections) in female CF-1 mice were significantly inhibited by S-allyl cysteine pretreatment, given 3 h prior to each carcinogen injection. These data indicate that the allyl group coupled to a single sulfur atom might play an important structural role in inhibition of DMH-induced colonic nuclear toxicity and carcinogenesis. OSCs containing allyl groups stimulated glutathione S-transferase activity in both the liver and colon. However, their saturated analogues stimulated little or no hepatic and colonic glutathione S-transferase activity. Induction of hepatic and colonic glutathione S-transferase might assist in detoxification of carcinogens and could be necessary for some aspects of chemoprevention.
Onion and garlic essential oils were previously shown to inhibit mouse skin tumor promotion, as were the enzymes, lipoxygenase, and cyclooxygenase. In the present study, the inhibition of soybean lipoxygenase (EC 1.13.11.12) by onion and garlic components and related compounds was investigated. The IC50 values as well as the kinetic inhibition constants were determined for the most active compounds. Di-(1-propenyl) sulfide, an analog of the substrate moiety required for oxygenase action, was the only irreversible inhibitor observed with Ki = 59 microM and k3 = 0.53/min. Inhibition in the presence of substrate was uncompetitive at 88 and 132 microM linoleic acid with Ki = 129 microM. At 173 microM linoleic acid, however, inhibition was competitive with Ki = 66 microM. Dially trisulfide, allyl methyl trisulfide, and diallyl disulfide were competitive inhibitors, while 1-propenylpropyl sulfide and (E, Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide (ajoene) were mixed inhibitors. Nordihydroguaiaretic acid (NDGA), the most potent lipoxygenase inhibitor, was a competitive inhibitor with Ki = 0.29 microM. The results indicate a relative potency of inhibition for structural features in the following order: di(1-propenyl) sulfide greater than an alkenyl trisulfide greater than an alkenyl disulfide. Di(n-propyl) disulfide, a major onion oil component, inhibited neither lipoxygenase nor promotion. Di(1-propenyl) sulfide and ajoene inhibited both. This suggests that the inhibition of lipoxygenase may be involved in antipromotion.
Experiments with Salmonella tester strains indicated that aqueous garlic extract possesses antimutagenic properties toward ionizing radiation, peroxides, adriamycin, and N-methyl-N'-nitro-nitrosoguanidine. The assumption that radical scavenging garlic constituents, i.e., molecules with sulfur moieties, might be responsible for the inhibitory effect of aqueous extract toward mutagenesis induced by radiation and radiomimetic compounds was confirmed by the results of subsequent experiments; 1) garlic extract attenuated the lethal effects of gamma-rays on repair-deficient E. coli strains; 2) the garlic constituent allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is partly responsible for the reduced radiation-induced mutagenesis in Salmonella typhimurium TA 102. No such inhibitory effects were detected with alliin (S-allyl-L-cysteine sulfoxide) or cysteine; 3) aqueous garlic extract inhibited hydrogen-peroxide-induced lipid peroxidation. Results obtained in preliminary experiments with Chinese hamster ovary cells suggest that the antimutagenic properties of garlic extract are not restricted to procaryotic cells.
Interviews with 564 patients with stomach cancer and 1,131 controls in an area of China where gastric cancer rates are high revealed a significant reduction in gastric cancer risk with increasing consumption of allium vegetables. Persons in the highest quartile of intake experienced only 40% of the risk of those in the lowest. Protective effects were seen for garlic, onions, and other allium foods. Although additional research is needed before etiologic inferences can be made, the findings are consistent with recent reports of tumor inhibition following administration of allium compounds in experimental animals.
Diallyl sulfide (DAS) is a principal thioether of garlic (Allium sativum) accounting, in part, for the flavor and fragrance of this herb. Previous studies have shown that DAS is a potent inhibitor of experimentally induced colon cancer in mice. Metabolic studies of other garlic-derived substances suggested that DAS could prevent tumorigenicity of other hepatic activated carcinogens. The present study was designed to determine whether DAS could inhibit the DNA-damaging and tumorigenic effects of N-nitrosomethylbenzylamine in rat esophagus. A dose of 200 mg/kg of DAS given p.o. 3 h prior to N-nitrosomethylbenzylamine administration was found to inhibit the carcinogen-induced nuclear toxicity by 64% to 56% at the two doses (3 and 5 mg/kg) of NMBA tested. These results suggested that the compound was potentially anticarcinogenic. In the carcinogenicity experiment it was found that DAS totally inhibited tumor formation in rats treated with a carcinogenic dose of NMBA (100% inhibition of papilloma and squamous cell carcinoma incidence, P less than 0.0001). Additionally DAS was found to substantially reduce hepatic microsomal metabolism of the carcinogen. These data demonstrate that DAS is unique in its anticarcinogenic activity. It strongly suppresses the tumorigenic effects of potent, metabolically activated monoalkylating carcinogens in the gastrointestinal tract.
Prostaglandin endoperoxide H synthase is the key enzyme in the conversion of arachidonic acid to tissue prostanoids. Two isoforms of prostaglandin endoperoxide H synthase have been identified: PHS-1 is constitutively expressed in most tissues under normal physiological conditions and PHS-2 is expressed in response to inflammatory agents, tumor promotors, and other agents related to mitogenesis. Previous work demonstrated that PHS-1 can activate arylamine carcinogens. We report here that PHS-2 can also activate an arylamine carcinogen to form DNA adducts. This is shown by: (1) use of purified ovine PHS-2 to form DNA adducts; (2) increased DNA adduct formation, PHS-2 mRNA, and PHS-2 protein after treatment of HUVEC cells with the PHS-2 inducer PMA; and (3) transient expression of PHS-2 cDNA in COS-1 cells gave rise to both elevations of PHS-2 enzyme protein and DNA adduct formation. Finally, two PHS inhibitors, aspirin and indomethacin, showed significant inhibition of PHS-2-mediated DNA adduct formation.
Previous studies have demonstrated that cytochrome P450 2E1 (P450 2E1) catalyzes the oxidation of acetone in vitro. The present study was designed to determine the importance of P450 2E1 in the catabolism of acetone in rats using diallyl sulfide (DAS) as an inhibitor of this enzyme. After a single intragastric dose of DAS, blood samples were collected from rats at different time points, and blood acetone concentrations were measured by gas chromatography. In a low DAS dose (50 mg/kg body weight) group, the maximum acetone level of 6-fold higher than the normal level was reached at 6 hr; the acetone level returned to normal at 48 hr. In a high dose (200 mg/kg) group, the maximum acetone level of 9-fold higher than the normal level was reached at 12 hr; the acetone level returned to normal at 60 hr. The turnover time and fractional turnover rate of elevated acetone were 15.8 +/- 0.5 hr and 0.054 +/- 0.001 hr-1, respectively, for the low dose, and 19.2 +/- 0.6 hr and 0.046 +/- 0.005 hr-1, respectively, for the high dose. In a chronic experiment, DAS (50 and 200 mg/kg, i.g.) was given to rats daily for 29 days, and elevated blood acetone levels were observed during the entire experimental period: 2.0 to 2.8 micrograms/mL for the low dose and 3.4 to 3.9 micrograms/mL for the high dose at 24 hr after the 1st, 7th, 14th and 28th doses versus 0.8 to 0.9 micrograms/mL for the control. The increase of blood acetone level was closely related to the decreases of N-nitrosodimethylamine (NDMA) demethylase activity and P450 2E1 content in liver microsomes. Consistent with the lack of cumulative effect from the multiple doses of DAS on acetone level, rather stable levels of the DAS metabolites, diallyl sulfoxide (45.0 micrograms/mL, range: 33.8 to 58.6 micrograms/mL) and diallyl sulfone (11.7 micrograms/mL, range: 6.9 to 15.6 micrograms/mL), were observed at 24 hr after the 1st, 7th, 21st and 28th doses with DAS (200 mg/kg) in the chronic experiment. It is likely that the inactivation and inhibition of P450 2E1 by DAS and its metabolites block the oxidation of acetone and cause its elevation in blood. The results strongly suggest an important role of P450 2E1 in acetone catabolism under physiological conditions.
Bioactivation of 14C-benzo(a)pyrene-7,8-dihydrodiol catalyzed by lipoxygenase purified from human term placenta of nonsmoking women and intrauterine conceptal tissues (at 4 weeks of gestation) was investigated. Incubation of 14C-benzo(a)pyrene-7,8-dihydrodiol with 3 mM linoleic acid in the presence of lipoxygenase purified from either human term placenta or intrauterine conceptal tissues resulted in co-oxidation generating several soluble and protein-bound metabolites of benzo(a)pyrene-7,8-dihydrodiol. The co-oxidation was inhibited significantly by the specific lipoxygenase inhibitor, nordihydroguaiaretic acid. Substitution for the active enzyme in the reaction mixture with heat denatured enzyme resulted in almost complete abolition of benzo(a)pyrene-7,8-dihydrodiol co-oxidation. These results suggest that lipoxygenase in the placentas and intrauterine conceptal tissues is capable of metabolizing benzo(a)pyrene-7,8-dihydrodiol to several reactive metabolites and may represent one of the major xenobiotic metabolizing pathways of bioactivating chemicals in the intrauterine compartment.
Ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide), a garlic-derived natural compound, which had been shown to have cytostatic/cytotoxic properties, was tested with a B cell lymphoma-derived cell line (BJA-B cells) in order to elucidate its mechanism of cytotoxic action. Viability of the cells was determined by the Trypan blue exclusion test and the colorimetric tetrazolium (MTT) assay, whereas metabolic disturbance was evaluated by measuring the pools of reduced (GSH), oxidized glutathione (GSSG) and the acidic amino acids, Glu and Asp. Fast uptake of ajoene was accompanied by an immediate reduction of the GSH and increase in the GSSG levels. The extent of these changes, as well as the further development of the metabolite pools, depended on the ajoene dose per cell. At a sublethal ajoene dose the GSH and GSSG pools rose at the later stages to levels much higher than in the control experiment. Bleb formation at the cytoplasmic membrane was a further rapid phenomenon, although injuries detected by Trypan blue exclusion developed only at a later stage. The MTT assay, performed in a parallel experiment (48 h after ajoene addition), showed, however, that reduction of cell viability was established at the very beginning of ajoene exposure. Altogether, the action of ajoene strongly resembled oxidative stress (i.e., interference with SH homeostasis and its pleiotropic consequences to cell physiology and metabolism.
Six organosulfur compounds found in garlic were examined for their ability to alter the growth of canine mammary tumor cells (CMT-13) in culture. Water-soluble organosulfur compounds (S-allyl-cysteine, S-ethyl-cysteine and S-propyl-cysteine) did not significantly alter the growth of CMT-13 cells when added to cultures at 1.0 mM or less. However, oil-soluble organosulfur compounds (diallyl sulfide, diallyl disulfide and diallyl trisulfide) markedly inhibited growth. Increasing addition of diallyl disulfide (DADS) resulted in a progressive decrease in CMT-13 cell growth. Addition of glutathione before DADS markedly decreased the severity of the growth inhibition. Treatment with DL-buthionine-SR-sulfoxamine, a specific inhibitor of glutathione synthesis, accentuated the growth inhibition caused by DADS. These studies show that some organosulfur compounds found in garlic are effective inhibitors of the growth of the neoplastic CMT-13 cell. The inhibitory effects of these compounds are modified by intracellular glutathione.
The present studies examined the impact of a processed garlic powder on the in vivo occurrence of DNA adducts caused by N-nitroso compounds (NOC) in rats. Addition of 2% garlic powder to diets containing aminopyrine and sodium nitrite (each at 600 mg/kg) reduced the occurrence of both 7-N-methyldeoxyguanosine (7-N-mG) and 6-O-methyldeoxyguanosine (6-O-mG) adducts to rat liver DNA by approximately 55%; and over 80% when 4% garlic was provided. Dietary supplementation with garlic powder (2 and 4%) also reduced the occurrence of 7-N-mG and 6-O-mG adducts by approximately 40 and 60% respectively, in rats intubated with N-nitrosodimethylamine (150 mg/kg body wt). The quantity of 7-N-mG and 6-O-mG adducts in mammary tissue of rats given intravenous N-methyl-N-nitrosourea (50 mg/kg body wt) was reduced over 50% in rats fed 2% garlic compared to controls. The depression in the occurrence of these adducts was approximately 70% when dietary garlic was increased to 4%. These experiments suggest the reduction in DNA adducts caused by processed garlic powder likely reflects a depression in the formation of NOC from precursors and changes in the bioactivation and/or denitrosation of NOC.
Our previous study demonstrated that diallyl sulfide (DAS), a compound derived from garlic, transcriptionally activated the P450 2B1/2 genes in rat liver. In the present study, rat primary hepatocytes were used to determine the effects of DAS and its metabolite, diallyl sulfone (DASO2), on the expression of the P450 2B1/2 genes. Freshly isolated adult rat hepatocytes were cultured in a serum-free medium on a reconstituted basement membrane matrix "matrigel" that enabled the hepatocytes to maintain expression of numerous liver-specific genes for more than 1 week. After 48-hr of acclimation, 0.1, 0.5, and 2.0 mM concentrations of DAS or DASO2 were added to the culture medium and the cells were harvested at 4, 12, 24, or 36 hr after the treatment for the preparation of microsomes and RNA. Cytotoxicity was not observed by morphological examinations after DAS and DASO2 treatments. In contrast to the in vivo results, there was only a slight increase in the levels of P450 2B1/2 mRNA and protein in DAS-treated cells. However, DASO2 treatment (2 mM) resulted in 11-, 21-, and 22-fold increases in P450 2B1/2 mRNA levels at 12, 24, and 36 hr after the treatment, respectively. P450 2B1/2 protein levels were also increased markedly in DASO2-treated cells. Co-incubation of the rat hepatocyte cultures with a physiological concentration of growth hormone significantly blocked the induction of P450 2B1/2 mRNA by DASO2. Northern blot analysis using oligonucleotide probes specific for 2B1 and 2B2 demonstrated that DASO2 induced mRNA levels of both 2B1 and 2B2, with a greater induction of 2B1 mRNA. For comparison, the effects of disulfiram (DSF) and its metabolite, diethyldithiocarbamate (DDTC), on P450 2B1/2 mRNA expression were also examined in the cultured rat hepatocytes. Both DSF and DDTC caused a significant increase in P450 2B1/2 mRNA level with the highest induction at 0.5 mM. Addition of growth hormone to the culture effectively suppressed the P450 2B1/2 mRNA induction by DSF but had little effect on the induction by DDTC. Neither mRNA nor protein levels of P450 2E1 in cultured hepatocytes were affected by all the organosulfur compounds tested. These results suggest that DASO2, DSF and DDTC selectively modulate P450 isozymes in cultured rat primary hepatocytes and that the induction of P450 2B1/2 by DAS in rat liver may be mediated by its metabolite, DASO2.
A sulfur-containing amino acid compound, S-allyl cysteine (SAC), derived from garlic extract inhibited proliferation of nine human and murine melanoma cell line in a dose-dependent manner (1.2-10 mM) assessed by a [3H]thymidine incorporation assay. Three control human lymphoblastoid cell lines were not inhibited by SAC concentrations < 5 mM. Four human melanoma cell lines in a soft-agar assay also showed dose-dependent inhibition of colony formation by SAC. Melanin content was increased up to 95% compared to the same untreated cell lines in these four human melanoma and two B16 murine melanoma sublines. Expression of cell surface gangliosides, cellular-differentiation and transformation markers, decreased after SAC treatment. Significant morphological changes including 'flattening and/or dendritic-like elongations' were also observed. Thus SAC inhibited cellular growth and proliferation and modulated major cell differentiation markers of melanoma.
Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water-soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P<0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P<0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P<0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU-induced mammary carcinogenesis.
Diallyl disulfide (DADS), an oil-soluble organosulfur compound in processed garlic, was more effective in inhibiting the in vitro growth of human tumor cell lines: HCT-15 (colon), A549 (lung), and SK MEL-2 (skin) than isomolar quantities of the water-soluble compound S-allyl cysteine (SAC). Addition of DADS (100 microM) was cytostatic to all three cell lines. The importance of the allyl and the disulfide groups were revealed by the lack of a comparable depression in the growth of HCT-15 cells exposed to its saturated analogue, dipropyl disulfide (DPDS). Treatment with DADS also resulted in a dose-dependent increase in intracellular free calcium in cells. A dose-dependent decrease in the activity of calcium-dependent ATPase enzyme occurred in HCT-15 cells exposed to increasing quantities of DADS. A correlation (r = -0.975) was found between the intracellular free calcium levels and the Ca-ATPase activity in DADS-treated cells. These studies document that DADS, a constituent of garlic oil, is an effective inhibitor of the growth of human neoplastic cells. Alterations in calcium hemostasis are likely involved in the growth inhibition/cytotoxicity caused by DADS.
Various dietary components were evaluated as factors influencing garlic's ability to depress rat mammary cell DNA adducts resulting from 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Diets with or without garlic powder (20 g/kg) were provided for 2 wk before DMBA treatment (25 mg/kg body weight). Rats fed diets containing 36 g casein/100 g diet had 31% fewer (P < 0.05) mammary cell DNA adducts than those fed 12 g/100 g. Garlic supplementation significantly (P < 0.05) reduced DNA adducts in rats fed either 12 or 36 g casein/100 g by 35 and 32% respectively. In the absence of dietary garlic, DNA adducts were 23% lower (P < 0.05) in rats provided a diet containing supplemental L-methionine at 0.9 g/100 g than at 0.3 g/100 g. However, adduct inhibition by garlic supplementation was greater in rats fed the lower (P < 0.05) amount of methionine (54 vs. 26% inhibition). Adduct levels in rats fed diets with 20 g corn oil/100 g were twice those occurring in rats fed 5 g/100 g (P < 0.05), regardless of adjustment for energy density. Garlic supplementation prevented the increase in DNA adducts caused by increasing dietary corn oil. Combining dietary supplements of garlic, selenite (0.5 mg/kg diet) and retinyl acetate (328 mg/kg diet) inhibited the occurrence of DNA adducts to a greater degree than when each was supplied individually. These studies demonstrate that while dietary garlic can reduce DNA adduct formation in mammary tissue caused by DMBA, this protection is influenced by several dietary components.
The present studies compared the effects of various oil-soluble compounds containing allyl and disulfide groups on the proliferation of cultured human colon tumor cells (HCT-15). Diallyl disulfide (DADS) was more effective in inhibiting the growth of HCT-15 cells than isomolar concentrations of S-allyl cysteine, dipropyl disulfide (DPDS), allyl chloride, allyl glycidyl ether and allyl alcohol. These studies clearly demonstrate the importance of both the diallyl and the disulfide groups in DADS. Treatment of HCT-15 cells with 100 microM DADS increased the intracellular calcium levels by 40%, while DPDS caused only a 12% increase in intracellular calcium. Exposure to 100 microM DADS or more, but not DPDS, caused the cells to undergo apoptosis as determined by morphological changes and DNA fragmentation. A positive correlation (r=0.944) was found between DADS-induced DNA fragmentation and its ability to increase intracellular free calcium levels. The widespread effectiveness of DADS was evident by its ability to inhibit the growth of human colon (HCT-15), skin (SK MEL-2) and lung (A549) tumor cell lines.
Sulfur-containing substances derived from garlic and onion have been shown to prevent experimental carcinogenesis. One of the hypotheses explaining the mechanisms of the chemopreventive activity of these substances is that they activate detoxification systems such as glutathione S-transferase (GST). In this study the effects of S-allylcysteine (SAC), a water-soluble organosulfur compound derived from garlic, on GST activities in the liver, small intestine and colon were investigated. Additionally, we examined SAC for chemopreventive effects on aberrant crypt foci, which are the most likely precursors of colon cancers. In the rat colonic aberrant crypt assay administration of SAC during the initiation period decreased the number of aberrant crypt foci by 33 and 54% in groups given 40 or 80% maximum tolerated dose (MTD) of SAC respectively. The number of aberrant crypt foci, however, was not changed when SAC was given during the promotion period. GST activity in the liver was increased significantly by 41% 12 h after a single oral administration of 3.5 mmol/kg SAC and this elevated GST level was maintained over a 72 h period. GST levels were increased significantly by the administration of SAC (1.8 mmol/kg/ day for 3 days) not only in the liver but also in the proximal and middle small bowel. Isozyme levels of GST after administration of SAC were also determined using Western blotting. Hepatic GST-alpha and GST-mu were significantly increased by 35 and 42% respectively after oral administration of SAC. GST-pi levels were lower than the detection limit (130 ng/mg/protein) in both the control and SAC-treated groups. These results strongly support the previous working hypothesis that SAC exhibits chemopreventive activity by exerting specific effects on carcinogen detoxification systems.
Three heterocyclic aromatic amines, 2-amino-3-methyl-imidazo[4, 5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, have been found in boiled pork juice. We have investigated the effect of naturally occurring organosulfur compounds, which are present in garlic and onion, on mutagen formation in boiled pork juice. Six organosulfur compounds - diallyl disulfide (DAD), dipropyl disulfide (DPD), diallyl sulfide (DAS), allyl methyl sulfide (AMS), allyl mercaptan (AM) and cysteine - were added separately to the pork juice before reflux boiling and then the mutagenicity of each sample was examined with the Salmonella typhimurium strain TA98 in the presence of S9 mix. All six compounds were found to inhibit the mutagenicity of boiled pork juice. The greatest inhibitory effect was observed with DAD and DPD, and this was 111-fold higher than that of the lowest, cysteine. To elucidate the inhibitory effect of DAD on mutagen formation in boiled pork juice, the major mutagenic fractions were monitored after HPLC separation by their mutagenicity with S. typhimurium TA98. By comparing the retention times of authentic IQ compounds from boiled pork juice with those following the addition of DAD, we showed that the mutagenicity of three major fractions was significantly inhibited compared with those same fractions in boiled pork juice alone. In addition, the Maillard reaction products (MRPs) in the boiled pork juice with and without the addition of DAD were quantified and identified by capillary gas chromatography and gas chromatography-mass spectrometry. The results show that the reduction in the total amount of MRPs (pyridines, pyrazines, thiophenes and thiazoles) in boiled pork juice after boiling for 12 h is correlated with their mutagenicity. Among the MRPs, tetrahydrothiophene-3-one exhibited the strongest correlation. These data suggest that the inhibition of IQ mutagen formation by DAD is mediated through the reduction of MRPs production.
In this study, we report a novel anticarcinogenic activity of an organosulfur compound from garlic, diallyl disulfide (DADS). DADS treatment significantly inhibited the growth of H-ras oncogene transformed tumors in nude mice. As compared to controls, the appearance of tumors was also delayed markedly by oral administration of DADS. The inhibition of tumor growth by DADS treatment correlated with the inhibition of p21H-ras membrane association in the tumor tissue. The levels of membrane associated p21H-ras were markedly lower in the tumor tissues of DADS treated mice as compared to controls. An opposite trend, however, was evident for cytosolic p21H-ras. Furthermore, DADS treatment resulted in a significant inhibition of hepatic as well as tumoral 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. These results indicate that DADS suppresses the growth of H-ras oncogene transformed tumors in nude mice by inhibiting the membrane association of tumoral p21H-ras.
We have studied the effect of aqueous extract of raw garlic and boiled garlic on cyclooxygenase activity in rabbit tissues. Raw garlic inhibited cyclooxygenase activity non-competitively and irreversibly. A dose-dependent inhibition of cyclooxygenase activity was observed in tissues treated with raw garlic. The garlic concentrations required for 50% inhibition of platelets, lung and vascular aortic cyclooxygenase activities of rabbits were 0.35, 1.10 and 0.90 mg, respectively. Cyclooxygenase activity of rabbit platelets was more sensitive to inhibition by raw garlic than the enzyme from blood vessels or lungs. Boiled garlic was found to have little effect on cyclooxygenase activity as compared to raw garlic in these tissues. This may be because the active component of raw garlic is destroyed upon heating. These results indicate that garlic may be beneficial in the prevention of thrombosis if ingested raw rather in a cooked form.
The anti-initiating properties of allyl sulfides on rat liver carcinogenesis induced by N-nitrosodiethylamine (NDEA) or aflatoxin B1 (AFB1) were evaluated by using a three-step medium-term hepatocarcinogenesis assay. Diallyl sulfide (DAS) or diallyl disulfide (DADS) was added to the diet of rats (2 g/kg) for three weeks, during which NDEA or AFB1 was administered by intraperitoneal injection. The rats were submitted later to eight days of 2-acetylaminofluorene administration and to two-thirds hepatectomy, then to phenobarbital administration. After eight weeks, liver preneoplastic foci expressing the placental form of glutathione S-transferase were detected. The results show that DAS and DADS strongly reduced the number and the size of preneoplastic foci initiated by NDEA and AFB1, but especially by AFB1; DADS is more efficient than DAS. Most likely, the inhibition of the first step of hepatocarcinogenesis by allyl sulfides is related to the modulating effects that these compounds exert on the enzymes involved in activation and/or detoxication of the carcinogens. Our study demonstrated the chemopreventive potencies of dietary allyl sulfides in liver carcinogenesis induced by two potent hepatic carcinogens.