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Medicinal Plants and Cancer Chemoprevention
... In addition, the stem bark of the plant contains phytochemicals such as saponins, flavonoids, tannins, and alkaloids. These compounds are responsible for the plant's antioxidant qualities and ability to reduce radicals like DPPH and NO [51,52]. Moreover, research has emphasised the defensive impact of F. platyphylla stem bark extract against liver injury caused by carbon tetrachloride. ...
It has been discovered that the plant Ficus platyphylla, which is employed in Togo and Nigerian traditional medicine, possesses antibacterial and wound-healing qualities. The plant's stem bark is rich in phytochemicals that support its antioxidant qualities, including saponins, flavonoids, tannins, and alkaloids. All of the fractions of Ficus platyphylla stem bark exhibited negative suppression of cell growth, according to a study on the subject. Compared to miconazole, the n-butanol fraction showed 90% reduction of antifungal activity against Fusarium lini. Nevertheless, none of the three fractions examined showed any signs of cytotoxic activity. Further chemical separation is required to fully comprehend the potential advantages of the plant
Mentha spicata, also called Mentha viridis, is a medicinal plant of the Lamiaceae family characterized by its potency to synthesize and secret secondary metabolites, essentially essential oils. Different populations use the aerial parts of this plant for tea preparation, and this tisane has shown several effects, according to ethnopharmacological surveys carried out in different areas around the world. These effects are attributed to different compounds of M. spicata, in which their biological effects were recently proved experimentally. Pharmacological properties of M. spicata extracts and essential oils were investigated for different health benefits such as antioxidant, anticancer, antiparasitic, antimicrobial, and antidiabetic effects. In vitro and in vivo studies showed positives effects that could be certainly related to different bioactive compounds identified in M. spicata. Indeed, volatile compounds seem to be efficient in inhibiting different microbial agents such as bacteria, fungi, and parasites through several mechanisms. Moreover, M. spicata exhibited, according to some studies, promising antioxidant, antidiabetic, anti-inflammatory, and anticancer effects, which show its potential to be used as a source for identifying natural drugs against cellular oxidative stress and its related diseases. Importantly, toxicological investigations of M. spicata show the safety of this species at different doses and several periods of use which justify its use in traditional medicines as tisane with tea. Here, we report, explore, and highlight the data published on M. spicata concerning its botanical description and geographical distribution, its phytochemical compounds, its pharmacological properties, and its toxicological investigations of M. spicata.
Citation: Soliman, M.S.M.; Abdella, A.; Khidr, Y.A.; Osman, H.G.O.; Al-Saman, M.A.; Elsanhoty, R.M. Pharmacological Activities and Characterization of Phenolic and Flavonoid Compounds in Methanolic Extract of Euphorbia cuneate Vahl Aerial Parts. Molecules 2021, 26, 7345.
Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.
Context: Euphorbia hierosolymitana is a member of Euphorbia species having a restricted use in traditional medicine in eastern Mediterranean countries. Aims: To phytochemically analyze different extracts of Euphorbia hierosolymitana and to investigate their anti-cancer activity against a panel of different cancer cell lines. Methods: The aerial parts of the plant were extracted by n-butanol and ethyl acetate. Each extract was subjected to Gas Chromatography-Mass Spectrometry (GC-MS) to determine the bioactive compounds. Additionally, the anti-cancer activity of each extract compared to positive control doxorubicin was evaluated against a panel of different cancer and normal cell lines by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Phytochemical analysis of the different extracts revealed different compounds of alkane hydrocarbons, fatty acids, sterols, phenols, glycosides, alkaloids, indol alkaloids, terpenoids, pyridine derivatives, and desulphosinigrin. Regarding anti-cancer activity, the n-butanol extract exhibited a significant selective concentration-dependent cytotoxicity in the colon cancer cell line (Caco-2) compared to other normal and cancer cell lines. This selective differential was comparable to the positive control, doxorubicin. The ethyl acetate extract, however, showed a significant cytotoxic activity among all the tested cell lines compared to the positive control. This cytotoxicity was in a concentration-dependent manner and weak to normal cell line (Wi38). Conclusions: The selective differential in anti-cancer activity between different types of extracts is attractive and holds significant promise for the development of new cancer therapies.
Medicinal plants serve as a lead source of bioactive compounds and have been an integral part of day-to-day life in treating various disease conditions since ancient times. Withaferin A (WFA), a bioactive ingredient of Withania somnifera, has been used for health and medicinal purposes for its adaptogenic, anti-inflammatory, and anticancer properties long before the published literature came into existence. Nearly 25% of pharmaceutical drugs are derived from medicinal plants, classified as dietary supplements. The bioactive compounds in these supplements may serve as chemotherapeutic substances competent to inhibit or reverse the process of carcinogenesis. The role of WFA is appreciated to polarize tumor-suppressive Th1-type immune response inducing natural killer cell activity and may provide an opportunity to manipulate the tumor microenvironment at an early stage to inhibit tumor progression. This article signifies the cumulative information about the role of WFA in modulating antitumor immunity and its potential in targeting prostate cancer.
Podophyllum hexandrum Royle [=Sinopodophyllum hexandrum (Royle) T.S. Ying] is an important, endemic medicinal plant species of Himalaya. It is used in Unani System of Medicine under the name of 'Papra'. The drug was not mentioned in previous literatures, but the first time it introduced in Unani Medicine by a great scholar Hakim Najmul Ghani. He has mentioned its uses and benefits in his classical book Khazainul Advia. In Unani Medicine the plant species has been used to treat various ailments like constipation, fever, jaundice, liver disorders, syphilis, diseases of lymph glands etc. In Kashmir Himalaya it is used to treat various diseases by local medicinemen, but now it is listed in rare drugs. Various pharmacological studies have been done such as antioxidant, antimicrobial, anti-inflammatory, antifungal, radio-protective etc., recently it has also been reported that podophyllotoxin or podophyllin can be used to treat some forms of cancers also.
In this paper we review the mechanisms of the antitumor effects of Hypericum perforatum L. (St. John’s wort, SJW) and its main active component hyperforin (HPF). SJW extract is commonly employed as antidepressant due to its ability to inhibit monoamine neurotransmitters re-uptake. Moreover, further biological properties make this vegetal extract very suitable for both prevention and treatment of several diseases, including cancer. Regular use of SJW reduces colorectal cancer risk in humans and prevents genotoxic effects of carcinogens in animal models. In established cancer, SJW and HPF can still exert therapeutic effects by their ability to downregulate inflammatory mediators and inhibit pro-survival kinases, angiogenic factors and extracellular matrix proteases, thereby counteracting tumor growth and spread. Remarkably, the mechanisms of action of SJW and HPF include their ability to decrease ROS production and restore pH imbalance in tumor cells. The SJW component HPF, due to its high lipophilicity and mild acidity, accumulates in membranes and acts as a protonophore that hinders inner mitochondrial membrane hyperpolarization, inhibiting mitochondrial ROS generation and consequently tumor cell proliferation. At the plasma membrane level, HPF prevents cytosol alkalization and extracellular acidification by allowing protons to re-enter the cells. These effects can revert or at least attenuate cancer cell phenotype, contributing to hamper proliferation, neo-angiogenesis and metastatic dissemination. Furthermore, several studies report that in tumor cells SJW and HPF, mainly at high concentrations, induce the mitochondrial apoptosis pathway, likely by collapsing the mitochondrial membrane potential. Based on these mechanisms, we highlight the SJW/HPF remarkable potentiality in cancer prevention and treatment.
Background
The chemical composition of Handal (Citrullus colocynthis L.) seed oil cultivated in Jordan deserts was characterized, and its bioactivity was evaluated.
Methods
The oil was extracted from the grinded seeds in 500 ml Soxhlet extractor for 24 hr using n‐hexane, and the recovered fatty acids were methylated with methanolic‐HCL. The fatty acid methyl esters (FAMEs) composition was analyzed using GC‐MS and GC‐FID. The anticancer activity associated with the oil was assessed against colon cancer cell lines (Caco‐2 and HCT‐116) and compared to its cytotoxicity on the human skin fibroblast. Multivariate analysis was used to determine relationship of the fatty acid composition with that of the anticancer activity.
Results
The results demonstrated that fatty acid composition of Citrullus colocynthis seed oil chiefly contains Linoleic acid, denoted as C18:2n6 (75%), followed by Palmitic acid C16:0 (8%), Stearic acid C18:0 (5%), and Oleic acid C18:1n9 (9%). It is demonstrated as an excellent source of essential fatty acids omega‐6 (e.g., Linoleic acid), whereas omega‐3 (e.g., α‐Linolenic acid) and hydroxy polyunsaturated fatty acids are found at small level. Interestingly, the oil exhibited reasonable anticancer effects against colorectal cancer cell lines with IC50 values varying between 4 and 7 mg/ml. The correlation test revealed a relationship between the fatty acid composition and the effectiveness on treatments.
Conclusions
Handal plant from Jordan appears to have very high level of Linoleic acid compared to other oils measured in different geographic locations and that there appears to be some anticancer activities associated with the fatty acid content of Handal seed oil.
Fruit-derived bioactive substances have been spotlighted as a regulator against various diseases due to their fewer side effects compared to chemical drugs. Among the most frequently consumed fruits, apple is a rich source of nutritional molecules and contains high levels of bioactive compounds. The main structural classes of apple constituents include polyphenols, polysaccharides (pectin), phytosterols, and pentacyclic triterpenes. Also, vitamins and trace elements complete the nutritional features of apple fruit. There is now considerable scientific evidence that these bioactive substances present in apple and peel have the potential to improve human health, for example contributing to preventing cardiovascular disease, diabetes, inflammation, and cancer. This review will focus on the current knowledge of bioactive substances in apple and their medicinal value for human health.
Increasing herbal formulations have been used to treat several diseases including cancer. W. somnifera (Ashwagandha) is one such plant the extracts of which have been tested against a number of ailments including cancer, which remains as one of the most dreadful diseases on the globe. The ever-increasing number of cancer related mortality demands the development of novel chemopreventive agents with minimum side effects. Different compounds isolated from various parts of the plant like root, stem, and leaves have been reported to display significant anti-cancerous and immunomodulating properties and thus can be used alone or in combination with other chemotherapeutic drugs for cancer treatment. Through this review, we highlight the importance of W. somnifera in countering the potential oncogenic signaling mediators that are modulated by active constituents of W. somnifera in a variety of cancer types. Further, we hope that active constituents of W. somnifera will be tested in clinical trials so that they can be used as an important adjuvant in the near future for the effective treatment of cancer.
Alternative treatments for neoplastic diseases with new drugs are necessary because the clinical effectiveness of chemotherapy is often reduced by collateral effects. Several natural substances of plant origin have been demonstrated to be successful in the prevention and treatment of numerous tumors. Rosmarinus officinalis L. is a herb that is cultivated in diverse areas of the world. There is increasing attention being directed towards the pharmaceutical capacities of rosemary, utilized for its anti-inflammatory, anti-infective or anticancer action. The antitumor effect of rosemary has been related to diverse mechanisms, such as the antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response and anti-inflammatory response, modification of specific metabolic pathways, and increased expression of onco-suppressor genes. In this review, we aim to report the results of preclinical studies dealing with the anticancer effects of rosemary, the molecular mechanisms related to these actions, and the interactions between rosemary and anticancer drugs. The prospect of utilizing rosemary as an agent in the treatment of different neoplastic diseases is discussed. However, although the use of rosemary in the therapy of neoplasms constitutes a fascinating field of study, large and controlled studies must be conducted to definitively clarify the real impact of this substance in clinical practice.
Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato-and nephrotoxicities of cisplatin.
Cancer is a noncommunicable disease with a high worldwide incidence and mortality rate. The National Cancer Institute of Thailand reports increasing cumulative incidence of breast, colorectal, liver, lung, and cervical cancers, accounting for more than 60% of all cancers in the kingdom. In this current work, we attempt to elucidate the phytochemical composition of the okra ( Abelmoschus esculentus (L.) Moench) seed extract (OSE) and study its anticancer activity, delivered in its native form as well as in the form of polymeric micelles with enhanced solubility, in three carcinoma cell lines (MCF-7, HeLa, and HepG2). The presence of flavonoid compounds in the OSE was successfully confirmed, and direct delivery had the highest cytotoxic effect on the breast cancer cell line (MCF-7), followed by the hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cell lines in that order, while its delivery in polymeric micelles further increased this effect only in the HepG2 cell line. The OSE’s observed cytotoxic effects on cancer cell lines demonstrated a dose and time-dependent cell proliferation and migration inhibition plausibly due to VEGF production inhibition, leading to apoptosis and cell death, conceivably due to the four flavonoid compounds noted in the current study, one of which was isoquercitrin. However, in view of the latter compound’s isolated effects being inferior to those observed by the OSE, we hypothesize that either isoquercitrin requires the biological synergy of any one or all of the observed flavonoids or any of the three in isolation or all in concert are responsible. Further studies are required to elucidate the nature of the three unknown compounds. Furthermore, as we encountered significant problems in dissolving the okra seed extract and creating the polymeric micelles, further studies are needed to devise a clinically beneficial delivery and targeting system.
The apple (Malus domestica [Suckow] Borkh.) is one of the most economically and culturally significant fruits in the world today, and it is grown in all temperate zones. With over a thousand landraces recognized, the modern apple provides a unique case study for understanding plant evolution under human cultivation. Recent genomic and archaeobotanical studies have illuminated parts of the process of domestication in the Rosaceae family. Interestingly, these data seem to suggest that rosaceous arboreal crops did not follow the same pathway toward domestication as other domesticated, especially annual, plants. Unlike in cereal crops, tree domestication appears to have been rapid and driven by hybridization. Apple domestication also calls into question the concept of centers of domestication and human intentionality. Studies of arboreal domestication also illustrate the importance of fully understanding the seed dispersal processes in the wild progenitors when studying crop origins. Large fruits in Rosaceae evolved as a seed-dispersal adaptation recruiting megafaunal mammals of the late Miocene. Genetic studies illustrate that the increase in fruit size and changes in morphology during evolution in the wild resulted from hybridization events and were selected for by large seed dispersers. Humans over the past three millennia have fixed larger-fruiting hybrids through grafting and cloning. Ultimately, the process of evolution under human cultivation parallels the natural evolution of larger fruits in the clade as an adaptive strategy, which resulted in mutualism with large mammalian seed dispersers (disperser recruitment).
Cancer accounts for millions of deaths every year and, due to the increase and aging of the world population, the number of new diagnosed cases is continuously rising. Although many progresses in early diagnosis and innovative therapeutic protocols have been already set in clinical practice, still a lot of critical aspects need to be addressed in order to efficiently treat cancer and to reduce several drawbacks caused by conventional therapies. Nanomedicine has emerged as a very promising approach to support both early diagnosis and effective therapy of tumors, and a plethora of different inorganic and organic multifunctional nanomaterials have been ad hoc designed to meet the constant demand for new solutions in cancer treatment. Given their unique features and extreme versatility, nanocarriers represent an innovative and easily adaptable tool both for imaging and targeted therapy purposes, in order to improve the specific delivery of drugs administered to cancer patients. The current review reports an in-depth analysis of the most recent research studies aiming at developing both inorganic and organic materials for nanomedical applications in cancer diagnosis and therapy. A detailed overview of different approaches currently undergoing clinical trials or already approved in clinical practice is provided.
There has been a renewed interest in the identification of natural products having premium pharmacological properties and minimum off-target effects. In accordance with this approach, natural product research has experienced an exponential growth in the past two decades and has yielded a stream of preclinical and clinical insights which have deeply improved our knowledge related to the multifaceted nature of cancer and strategies to therapeutically target
deregulated signaling pathways in different cancers. In this review, we have set the spotlight on the scientifically proven ability of berberine to effectively target a myriad of deregulated pathways.
Malus domestica distributes around 20 countries all over the world and normally in India, Asia, Africa, North & South America, and Europe. In India it is commonly seen in Uttaranchal appear during the late summer months, Jammu and Kashmir's apple season may stretch into late November.Malus domestica(Family-Rosaceae) are widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apple with reduced risk of some cancer, cardiovascular disease,obesity, pulmonary dysfunction, asthma and diabetes. Apple has been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol.The paper reviews on its pharmacological activities such as antiproliferative,anti-depressant, anti-inflammatory, anti-microbial.
In this study, taking into consideration the limitations of the current treatments of glioblastoma multiforme, we fabricated a biomimetic lipid-based magnetic nanovector with good loading capacity and a sustained release profile of the encapsulated chemotherapeutic drug, temozolomide. These nanostructures demonstrated an enhanced release after exposure to an alternating magnetic field, and a complete release of the encapsulated drug after the synergic effect of low pH (4.5), increased concentration of hydrogen peroxide (50 μM), and increased temperature due to the applied magnetic field. In addition, these nanovectors presented excellent specific absorption rate values (up to 1345 W/g) considering the size of the magnetic component, rendering them suitable as potential hyperthermia agents. The presented nanovectors were progressively internalized in U-87 MG cells and in their acidic compartments (i.e., lysosomes and late endosomes) without affecting the viability of the cells, and their ability to cross the blood-brain barrier was preliminary investigated by using an in vitro brain endothelial cell-based model. When stimulated with alternating magnetic fields (20 mT, 750 KHz), the nanovectors demonstrated their ability to induce mild hyperthermia (43°C) and strong anticancer effects against U-87 MG cells (scarce survival of cells characterized by low proliferation rate and high apoptosis levels). The optimal anticancer effects resulted from the synergic combination of hyperthermia chronic stimulation with the controlled temozolomide release, highlighting therefore the potential of the proposed drug-loaded lipid magnetic nanovectors for the treatment of glioblastoma multiforme.
Patients treated with conventional cancer chemotherapy suffer from side effects of the drugs due to non-selective action of chemotherapeutic drugs to normal cells. Active targeting nanoparticles that are conjugated to targeting ligands on the surface of nanoparticles play an important role in improving drug selectivity to the cancer cell. Several chemotherapeutic drugs and traditional/herbal medicines reported for anticancer activities have been investigated for their selective delivery to cancer cells by active targeting nanoparticles. This systematic review summarizes reports on this application. Literature search was conducted through PubMed database search up to March 2017 using the terms nanoparticle, chemotherapy, traditional medicine, herbal medicine, natural medicine, natural compound, cancer treatment, and active targeting. Out of 695 published articles, 61 articles were included in the analysis based on the predefined inclusion and exclusion criteria. The targeting ligands included proteins/peptides, hyaluronic acid, folic acid, antibodies/antibody fragments, aptamer, and carbohydrates/polysaccharides. In vitro and in vivo studies suggest that active targeting nanoparticles increase selectivity in cellular uptake and/or cytotoxicity over the conventional chemotherapeutic drugs and non-targeted nanoparticle platform, particularly enhancement of drug efficacy and safety. However, clinical studies are required to confirm these findings.
Leaves of Plantago lanceolata were traditionally used to treat wounds, burns, inflammations, fevers, diabetes and cancer. The present study was carried out on the phytochemical investigation and antimicrobial activities of the leaves extract of Plantago lanceolata since the plant was used for wound healing in Ethiopia. The powdered leaves of Plantago lanceolata herb was sequentially extracted with organic solvents: petroleum ether, chloroform/methanol (1:1) and methanol respectively. The crude extracts was subjected to phytochemical screening and revealed the presence of steroids, alkaloids, flavonoids, saponins, glycosides, phenols, tannins and terpenoids compounds that might be responsible for the claimed activities by local people. The petroleum ether extract was purified over silica gel preparative thin layer chromatography and yielded an isolated compound PL-5. The structure of this compound was elucidated using different spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR and DEPT-135 spectral data and by comparing the data with literature reports. The crude extracts, isolated pure compound and n-hexane extracted oil were tested against four bacterial species (Gram negative bacteria: Escherichia coli and Salmonela thyphei; Gram positive bacteria: Staphylococcus aureus, Streptococcus agalactiae) and two fungal species (Aspergillus niger and Fusarium solani) using paper disc diffusion method. All crude extracts, isolated pure compounds and extracted oil were active against all the tested bacterial. Additionally, petroleum ether and chloroform/methanol (1:1) crude extracts and n-hexane extracted oil were active against the two fungal species and hence the present work supported the medicinal use of Plantago lanceolata.
Objective(s)
Cucurbitacins exhibit a range of anti-cancer functions. We investigated the effects of cucurbitacins D, E, and I purified from Ecballium elaterium (L.) A. Rich fruits on some apoptotic and autophagy genes in human gastric cancer cell line AGS.
Materials and Methods
Using quantitative reverse transcription PCR (qRT-PCR), the expression of LC3, VEGF, BAX, caspase-3, and c-MYC genes were quantified in AGS cells 24 hr after treatment with cucurbitacins D, E, and I at concentrations 0.3, 0.1 and 0.5 μg/ml, respectively. Cell cycle and death were analyzed by flflowcytometry.
Results
Purified cucurbitacins induced sub-G1 cell-cycle arrest and cell death in AGS cells and upregulated LC3mRNA effectively, but showed a very low effect on BAX, caspase-3, and c-MYC mRNA levels. Also after treatment with cucurbitacin I at concentration 0.5 μg/ml, VEGF mRNA levels were increased about 4.4 times. Pairwise comparison of the effect of cucurbitacins D, E, and I on LC3 mRNA expression showed that the cucurbitacin I effect is 1.3 and 1.1 times that of cucurbitacins E and D, respectively; cucurbitacin D effect is 1.2 times that of cucurbitacin E (P-value <0.05). In silico analysis showed that among autophagy genes, LC3 has an important gastric cancer rank relation.
Conclusion
Cucurbitacins D, E, and I purified from E. elaterium fruits upregulate LC3 and induce sub-G1 cell-cycle arrest and cell death in human gastric cancer cell line AGS. Cucurbitacin I effect on LC3 mRNA expression is significantly more than that of cucurbitacins E and D.
Extracellular vesicles (EVs) are membranous vesicles released from almost all type of cells including cancer cells. EVs transfer their components, such as microRNAs (miRNAs), messenger RNAs, lipids and proteins, from one cell to another, affecting the target cells. Emerging evidence suggests that reciprocal interactions between cancer cells and the cells in their microenvironment via EVs drive disease progression and therapy resistance. Therefore, understanding the roles of EVs in cancer biology will provide us with new opportunities to treat patients. EVs are also useful for monitoring disease processes. EVs have been found in many kinds of biological fluids such as blood, urine, saliva and semen. Because of their accessibility, EVs offer ease of collection with minimal discomfort to patients and are preferred for serial collection. In addition, they reflect and carry dynamic changes in disease, allowing us to access crucial molecular information about the disease status. Therefore, EVs hold great possibility as clinically useful biomarkers to provide multiple non-invasive snapshots of primary and metastatic tumors. In this review, we summarize current knowledge of miRNAs in EVs in cancer biology and as biomarkers. Furthermore, we discuss the potential of miRNAs in EVs for clinical application.
Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.
Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.
Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications.
Ethnopharmacology relevance
Mentha spicata L (Lamiaceae), commonly called Spearmint, is wildly cultivated worldwide for its remarkable aroma and commercial value. In addition to traditional foods flavouring agent, M. spicata is well known for its traditional medicinal uses, particularly for the treatment of cold, cough, asthma, fever, obesity, jaundice and digestive problems.
Aim of the review: This review aims to critically appraise scientific literature regarding the traditional uses, bioactive chemical constituents and pharmacological activities of M. spicata.
Materials and methods
A review of the literature information on M. spicata was searched from scientific electronic search databases (Google Scholar, PubMed, Web of Science, ACS, Science Direct, Taylor and Francis, Wiley, Springer and SCOPUS. Structures for secondary metabolites were confirmed using PubChem and ChemSpider.
Results
The studies conducted on either crude extracts, essential oil or isolated pure compounds from M. spicata had reported a varied range of biological effects including antibacterial, antifungal, antioxidant, hepatoprotective, antidiabetic, cytotoxic, anti-inflammatory, larvicidal activity, antigenotoxic potential and antiandrogenic activities. Phytochemical analysis of various parts of M. spicata revealed 35 chemical constituents, belonging to phenolic acids, flavonoids and lignans.
Conclusion
The review finding indicates that the pharmacological properties of M. spicata supported its traditional uses. The essential oils and extracts showed remarkable antimicrobial, antioxidant, anticancer, anti-inflammatory and hepatoprotective activities. However, more studies, especially in vivo experiments and clinical trials of the human to evaluate cellular and molecular mechanisms based pharmacological, bioactive effectiveness and safety investigation, should be undertaken in the future to provide stronger scientific proof for their traditional medicinal properties.
The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by 7,12-dimethylbenz(a) anthracene (DMBA) in young Balb/c mice. Plant extracts were administered to animals orally, once/day (100mg/kg, 5 days/week) for the 20 weeks. Anticancer activity was examined via tumor progression, where antimutagenic activity was measured using 8-OHdG and sister chromatid exchange (SCE) levels. Eucalyptus camaldulensis Dehnh. leaves extract and Silybum marianum L. leaves extract significantly reduced 8-OHdG in cultured human lymphocytes in a dose-response manner (P<0.05). Similarly, the leave extracts of both plants significantly reduced chromosomal damage as measured by SCE levels (P<0.05). In the skin painting assay, the leave extracts of both plants significantly delayed the onset of tumors compared to DMBA treated group (P<0.05). The Silybum marianum leaves extract significantly reduced tumor incidence (P<0.01) and papilloma frequency (P<0.01) induced by DMBA. The Eucalyptus camaldulensis leaves extract significantly reduced the number of tumors per animal (P<0.05) and incidence of tumors (P<0.001). The in vitro and in vivo findings showed that leaves of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. extracts might be a promising source for anticancer and antimutagenic agents against human cancer.
Objective
Hypericum perforatum L also known as St. John’s wort is known to have many beneficial properties for the organism including its antioxidant and anticancer activities. It is also known to have shown antiproliferative and cytotoxic effects against various cancer cell lines. The purpose of this study was to investigate the effects of Hypericum perforatum L on 7,12-dimethylbenz(a)anthracene-induced rat oral squamous cell carcinoma model.
Design
The in vitro antioxidant properties of Hypericum perforatum L was determined and an extract was prepared. Thirty Wistar male rats were divided randomly into 4 groups (Control group, DMBA group, HP + DMBA group, HP group). The antioxidant defense mechanisms in tissue and blood samples were evaluated biochemically and immunohistochemically, the carcinomatous changes in connective tissue were investigated immunohistochemically and epithelial changes in the tissue samples were evaluated histopathologically.
Results
The extract revealed inhibitory effects on some antioxidant enzymes (catalase, glutathione peroxidase). Immunohistochemical evaluations revealed no invasive changes in the connective tissue. Hypericum perforatum L demonstrated chemopreventive effects although it did not prevent carcinomatous changes altogether.
Conclusions
Hypericum perforatum L is a promising chemopreventive agent and further studies are needed in order to evaluate the full potential of this plant.
This work is a bibliographical review of rosemary (Rosmarinus officinalis) that focuses on the application of derivatives of this plant for cosmetic products, an application which has been recognized and valued since Ancient Egyptian times. Rosemary is a plant of Mediterranean origin that has been distributed throughout different areas of the world. It has many medicinal properties, and its extracts have been used (mainly orally) in folk medicine. It belongs to the Labiatae family, which contains several genera-such as Salvia, Lavandula, and Thymus-that are commonly used in cosmetics, due to their high prevalence of antioxidant molecules. Rosemary is a perennial shrub that grows in the wild or is cultivated. It has glandular hairs that emit fragrant volatile essential oils (mainly monoterpenes) in response to drought conditions in the Mediterranean climate. It also contains diterpenes such as carnosic acid and other polyphenolic molecules. Herein, the botanical and ecological characteristics of the plant are discussed, as well as the main bioactive compounds found in its volatile essential oil and in leaf extracts. Afterward, we review the applications of rosemary in cosmetics, considering its preservative power, the kinds of products in which it is used, and its toxicological safety, as well as its current uses or future applications in topical preparations, according to recent and ongoing studies.
Withania somnifera, commonly known as "Ashwagandha" or "Indian ginseng" is an essential therapeutic plant of Indian subcontinent regions. It is regularly used, alone or in combination with other plants for the treatment of various illnesses in Indian Systems of Medicine over the period of 3,000 years. Ashwagandha (W. somnifera) belongs to the genus Withania and family Solanaceae. It comprises a broad spectrum of phytochemicals having wide range of biological effects. W. somnifera has demonstrated various biological actions such as anti-cancer, anti-inflammatory, anti-diabetic, anti-microbial, anti-arthritic, anti-stress/adaptogenic, neuro-protective, cardio-protective, hepato-protective, immunomodulatory properties. Furthermore, W. somnifera has revealed the capability to decrease reactive oxygen species and inflammation, modulation of mitochondrial function, apoptosis regulation and improve endothelial function. Withaferin-A is an important phytoconstituents of W. somnifera belonging to the category of withanolides been used in the traditional system of medicine for the treatment of various disorders. In this review, we have summarized the active phytoconstituents, pharmacologic activities (preclinical and clinical), mechanisms of action, potential beneficial applications, marketed formulations and safety and toxicity profile of W. somnifera.
Ethnopharmacological relevance
Withania somnifera (L.) Dunal (WS) is one of the most-studied Rasayana botanicals used in Ayurveda practice for its immunomodulatory, anti-aging, adaptogenic, and rejuvenating effects. The botanical is being used for various clinical indications, including cancer. Several studies exploring molecular mechanisms of WS suggest its possible role in improving clinical outcomes in cancer management. Therefore, research on WS may offer new insights in rational development of therapeutic adjuvants for cancer.
Aim of this review
The review aims at providing a detailed analysis of in silico, in vitro, in vivo and clinical studies related to WS and cancer. It suggests possible role of WS in regulating molecular mechanisms associated with carcinogenesis. The review discusses potential of WS in cancer management in terms of cancer prevention, anti-cancer activity, and enhancing efficacy of cancer therapeutics.
Material and methods
The present narrative review offers a critical analysis of published literature on WS studies in cancer. The reported studies were analysed in the context of pathophysiology of cancer, commonly referred as ‘cancer hallmarks’. The review attempts to bridge Ayurveda knowledge with biological insights into molecular mechanisms of cancer.
Results
The critical analysis suggests an anti-cancer potential of WS with a key role in cancer prevention. The possible mechanisms for these effects are associated with the modulation of apoptotic, proliferative, and metastatic markers in cancer. WS can attenuate inflammatory responses and enzymes involved in invasion and metastatic progression of cancer.
The properties of WS are likely to be mediated through withanolides, which may activate tumor suppressor proteins to restrict proliferation of cancer cells, regulate the genomic instability, and energy metabolism of cancer cells. The reported studies indicate the need for deeper understanding of molecular mechanisms of WS in inhibiting angiogenesis and promoting immunosurveillance. Additionally, WS can augment efficacy and safety of cancer therapeutics.
Conclusion
The experimentally-supported evidence of immunomodulatory, anti-cancer, adaptogenic, and regenerative attributes of WS suggest its therapeutic adjuvant potential in cancer management. The adjuvant properties of withanolides can modulate multidrug resistance and reverse chemotherapy-induced myelosuppression. These mechanisms need to be further explored in systematically designed translational and clinical studies that will pave the way for integration of WS as a therapeutic adjuvant in cancer management.
Today, pharmacognosy is considered a valuable science in the prevention and treatment of diseases. Among herbals, Berberine is an isoquinoline alkaloid found in the Berberis species. Surprisingly, it shows antimicrobial, antiviral, antidiarrheal, antipyretic, and anti‐inflammatory potential. Furthermore, it diminishes drug resistance in cancer therapy and enhances tumor suppression in part through autophagy and cell cycle arrest mechanisms. In the present review, we discuss the effect of berberine on diverse cellular pathways and describe how berberine acts as an autophagy modulator to adjust physiologic and pathologic conditions and diminishes drug resistance in cancer therapy.
Pulmonary delivery of drug nanocarriers can overcome the shortcomings of systemic cancer therapy via the enhanced permeability and retention (EPR) based-nanomedicine. Herein, inhalable multi-compartmental nanocomposites with the capability for both localized and modulated release of the hydrophobic mTOR inhibitor, rapamycin (RAP) and the hydrophilic herbal drug, berberine (BER) have been developed for lung cancer therapy. Two types of multi-compartmental nanocarriers were fabricated by enveloping BER hydrophobic ion pair-lipid nanocore within a shell of RAP-phospholipid complex bilayer to reduce the delivery gap between the two drugs. To further enhance their tumor targeting, the nanocarriers were layer-by-layer coated by cationic lactoferrin and anionic hyaluronate resulting in enhanced internalization and cytotoxicity against lung cancer cells. The inhalable nanocomposites fabricated by spray-drying of multi-compartmental nanocarriers exhibited favorable aerosolization efficiency (MMAD of 3.28 µm and FPF of 55.5%). The powerful anti-cancer efficacy of inhalable nanocomposites in lung cancer bearing mice compared to the inhaled free drugs was revealed by remarkable decrease in lung weight, and reduction in both number and diameters of lung adenomatous foci and angiogenic markers compared to positive control. Overall, localized delivery of RAP and BER to tumor cells via inhalable multi-compartmental nanocomposites holds great promise in management of lung cancer.
Background:
Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system.
Methods:
Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient's autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains. This T-cell genetic modification may occur either via viral-based gene transfer methods or non-viral methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation.
Results:
Clinical trials have shown very promising results in end-stage patients with a full recovery of up to 92% in Acute Lymphocytic Leukemia. Despite such results in hematological cancers, the effective translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within tumors.
Conclusion:
In this review, the basic design of CARs, the main genetic modification strategies, the safety matters as well as the initial clinical experience with CAR T-cells are described.
Immunotherapy is now the fourth pillar of cancer therapy, with surgery, radiation, and traditional chemotherapy being the remaining pillars. Over the past decade, enthusiasm for immunotherapy has increased because of, in part, data showing that it consistently improves overall survival in select patients with historically refractory cancers. This issue covers various aspects of immunotherapy ranging from use of 1) chimeric antigen receptor (CAR) T cells to treat patients with B-cell acute lymphoblastic leukemia; 2) population pharmacokinetic/dynamic modeling to develop new immune checkpoint inhibitors; and 3) simulations of existing population pharmacokinetic models of immunotherapy to minimize waste without compromising exposure and efficacy.
The mTOR pathway plays a crucial role in many human diseases, mostly associated with an over hyperactivity of the mTOR signaling, which makes its inhibitors potentially effective therapeutics. Thus, it is important to consider not only the mTOR pathway, but also all those factors that play a key role in its regulation, such as SIRT1 and AMPK. We previously demonstrated the role of some nutraceutical SIRT1 modulators in AMPK and mTOR pathway, showing the presence of a synergistic effect. Now we take further our research by evaluating the effect of berberine, quercetin, tyrosol and ferulic acid on the mTOR/S6K1/4E-BP1 signaling, along with the existence of any synergistic effect between the following associations: berberine+tyrosol, tyrosol+ferulic acid, ferulic acid + quercetin. Our results indicate the existence of an important relationship between the substances tested and the pathway of mTOR/S6K1/4E-BP1, a report corroborated by the bond of mTOR with SIRT1/AMPK pathways and by their reciprocal regulation.
Cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumour might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumour-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity). Heterogeneity provides the fuel for resistance; therefore, an accurate assessment of tumour heterogeneity is essential for the development of effective therapies. Multiregion sequencing, single-cell sequencing, analysis of autopsy samples, and longitudinal analysis of liquid biopsy samples are all emerging technologies with considerable potential to dissect the complex clonal architecture of cancers. In this Review, we discuss the driving forces behind intratumoural heterogeneity and the current approaches used to combat this heterogeneity and its consequences. We also explore how clinical assessments of tumour heterogeneity might facilitate the development of more-effective personalized therapies.
Exosomes have recently emerged as a promising drug delivery system with low immunogenicity, high biocompatibility, and high efficacy of delivery. We demonstrated earlier that macrophage-derived exosomes (exo) loaded with a potent anticancer agent paclitaxel (PTX) represent a novel nanoformulation (exoPTX) that shows high anticancer efficacy in a mouse model of pulmonary metastases. We now report the manufacture of targeted exosome-based formulations with superior structure and therapeutic indices for systemic administration. Herein, we developed and optimized a formulation of PTX-loaded exosomes with incorporated aminoethylanisamide-polyethylene glycol (AA-PEG) vector moiety to target the sigma receptor, which is overexpressed by lung cancer cells. The AA-PEG-vectorized exosomes loaded with PTX (AA-PEG-exoPTX) possessed a high loading capacity, profound ability to accumulate in cancer cells upon systemic administration, and improved therapeutic outcomes. The combination of targeting ability with the biocompatibility of exosome-based drug formulations offers a powerful and novel delivery platform for anticancer therapy.
The bioavailability of an orally administered drug primarily depends on its solubility in the GIT and its permeability across cell membranes. Also, a drug in solution form is preferred for conducting pharmacological, toxicological and pharmacokinetic studies during the drug development stage. Thus, poor water solubility not only limits a drug’s biological application but also challenges its pharmaceutical development. The use of lipid nanoparticles (LNs) in pharmaceutical technology has been reported for several years due to its important in green chemistry for several reasons specifically for its biochemical as “green” materials and biochemical processes as green processes that can be very environmentally friendly. Also, the physiological/physiologically related lipids (GRAS) made LNs usually enhance the drug absorption in the GIT. Hence, the pathways for absorption, metabolism, and transportation are present in the body, which may contribute to a large extent to the bio-fate of the lipidic carrier. Moreover, the LNs improves the mucosal adhesion and increases their GIT residence time. The LNs with a solid matrix are two types: solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC). Also, their hydrophobic core provides a suitable environment for entrapment of hydrophobic drugs to improve its bioavailability. This review highlights and discusses the simple and easily scaled-up novel SLN and NLC along with their different production techniques, hurdles, and strategies for the production of LNs, characterization, lyophilization and drug release. Also, this review summarizes the research findings reported by the different researchers regarding the different method of preparation, excipients and their significant findings.
Natural products (NPs) are secondary metabolites produced and used by organisms for defending or adapting purposes. These molecules were naturally selected during thousands of years to improve the specificity and cover a very wide range of functions, depending on the origin, the habitat and the specific activity carried out in the organism of origin. Due to these intrinsic features, NPs have been used as healing agents since thousands of years and still today continue to be the most important source of new potential therapeutic preparations.The purpose of this review is to provide information about the historical evolution of the NPs investigation methods, focusing attention on the relative benefit/problems emerged after the improvement of the scientific investigations about them, especially over the last two centuries. Taken together, the reported information lead to the central role of NPs in the future of drug development for human needs.