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Abstract

Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although, not yet completely understood, many mechanisms of anti‐cancer activity at the steps of cancer initiation, promotion and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro‐growth, ‐survival, ‐inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their anti‐tumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden. This article is protected by copyright. All rights reserved

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... Głównym zadaniem tego enzymu jest rozkład wiązania β-tioglukozydowego [9]. W wyniku działania mirozynazy powstaje cząsteczka glukozy oraz niestabilny związek tiohydroksym-O-sulfonowy, który jest przekształcany do tiocyjanianów, izotiocyjanianów oraz nitryli, w zależności od pH roztworu Analiza zawartości tiocyjanianów w wybranych warzywach krzyżowych [3,10]. Hydroliza glukozynolanów do tiocyjanianów, nitryli i izotiocyjanianów jest możliwa pod wpływem mirozynazy [2,10]. ...
... W wyniku działania mirozynazy powstaje cząsteczka glukozy oraz niestabilny związek tiohydroksym-O-sulfonowy, który jest przekształcany do tiocyjanianów, izotiocyjanianów oraz nitryli, w zależności od pH roztworu Analiza zawartości tiocyjanianów w wybranych warzywach krzyżowych [3,10]. Hydroliza glukozynolanów do tiocyjanianów, nitryli i izotiocyjanianów jest możliwa pod wpływem mirozynazy [2,10]. Na proces omówiony powyżej oprócz pH wpływają również białko epitiospecyficzne (ESP) oraz jony metali [3,10]. ...
... Hydroliza glukozynolanów do tiocyjanianów, nitryli i izotiocyjanianów jest możliwa pod wpływem mirozynazy [2,10]. Na proces omówiony powyżej oprócz pH wpływają również białko epitiospecyficzne (ESP) oraz jony metali [3,10]. Mirozynaza jest enzymem termo wrażliwym, lecz jej inaktywacja zachodzi w temperaturze 90°C, np. ...
Article
Przedmiot badań Warzywa krzyżowe (Cruciferae) to grupa roślin będąca popularnym elementem w diecie Polaków. Do warzyw krzyżowych należą m.in: kapusta głowiasta, brokuł, kalafior, brukselka, jarmuż, szpinak oraz rzepak. Rośliny krzyżowe są przedmiotem zainteresowania medycyny ze względu na ich aktywność przeciwnowotworową. Działanie chemoprewencyjne związane jest z obecnością glukozynolanów i produktów ich hydrolizy: tiocyjanianów, izotiocyjanianów i nitryli. Związki te zapobiegają rozwojowi nowotworów: piersi, płuc, prostaty oraz jelita grubego. Jednak nadmierne spożycie tiocyjanianów może skutkować zmniejszonym wytwarzaniem hormonów tarczycy. W dostępnym piśmiennictwie brakuje danych dotyczących ilości tiocyjanianów w warzywach krzyżowych oraz ilości ich spożycia przez Polaków. Cel badań Celem pracy badawczej było oznaczenie zawartości tiocyjanianów i porównanie ich w dziewięciu warzywach krzyżowych (Cruciferae). Materiał badany stanowiła kapusta głowiasta, kalafior, brokuł, szpinak, jarmuż, brukselka, kapusta pekińska oraz pak choi i kiełki brokułu. Ponadto celem było również porównanie zawartości tiocyjanianów w obrębie jadalnych różnych części tej samej rośliny (liście i łodygi kapusty pekińskiej i pak choi) oraz porównanie zawartości tiocyjanianów w kiełkach brokułu, jak również w jego różyczkach. Materiał i metody W badaniach wykorzystano metodę kolorymetryczną. Ekstrakcja tiocyjanianów była prowadzona z zastosowaniem 5 % kwasu trichlorooctowego. Tiocyjaniany w środowisku kwaśnym reagując z jonami Fe3+ tworzą kompleksy o krwistoczerwonym zabarwieniu. Produktami reakcji są kompleksy od Fe(SCN)2+ do Fe(SCN)63-. Pomiary absorbancji zostały wykonane przy użyciu spektrofotometru UV-VIS przy długości fali 470 nm. Wyniki Stężenie tiocyjanianów oznaczonych w warzywach krzyżowych było zróżnicowane, jednak najczęściej mieściło się ono między 10 ÷ 20 mg/kg s.m. Spośród badanych warzyw krzyżowych najwyższą zawartość tiocyjanianów oznaczono w szpinaku (0,420 mg/100 g świeżej masy) oraz w kiełkach brokułu (0,295 mg/100 g świeżej masy). Liście kapusty pekińskiej oraz pak choi były bogatszym źródłem tiocyjanianów niż ich łodygi. Stężenie tiocyjanianów w kiełkach brokułu było kilkukrotnie wyższe niż w różyczkach brokułu. Wnioski Badania pokazały, że stężenie tiocyjanianów różni się w obrębie tej samej rośliny. Zawartość tiocyjanianów jest różna w zależności od badanej tkanki roślinnej. W przeprowadzonym badaniu najbogatszym w tiocyjaniany warzywem krzyżowym był szpinak. Ze względu na około sześciokrotnie wyższe stężenie tiocyjanianów w liściach kapusty białej i pak choi niż w ich łodygach, korzystniejsze jest przyrządzanie potraw z wykorzystaniem liści kapusty.
... Glucosinolates are inert, anionic organic compounds, characterized by β-Dthioglucose, a sulfated oxime group (C=NOSO3 − ), and a variable side chain (-R), which will classify the glucosinolate as aliphatic, aromatic, or indole [15]. In response to mechanical or chemical stress, the glycosidic bond of the β-D-thioglucose present in glucosinolates is broken by the enzyme myrosinase, after which this compound converts to isothiocyanates, thiocyanates, and nitriles [16]. The amount of each product formed in this reaction can vary according to the specific proteins, pH, and/or temperature [12,16]. ...
... In response to mechanical or chemical stress, the glycosidic bond of the β-D-thioglucose present in glucosinolates is broken by the enzyme myrosinase, after which this compound converts to isothiocyanates, thiocyanates, and nitriles [16]. The amount of each product formed in this reaction can vary according to the specific proteins, pH, and/or temperature [12,16]. In Figure 2a, the described process is outlined. ...
... However, it is known that after specific doses, PEITC can be considered to be toxic and interact with other drugs that are being taken simultaneously. According to Abbaoui et al. (2018), for therapeutic effects, non-toxic doses of PEITC are sufficient, being safe for human consumption [16]. ...
Article
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The incidence of gastrointestinal pathologies (cancer in particular) has increased progressively, with considerable morbidity and mortality, and a high economic impact on the healthcare system. The dietary intake of natural phytochemicals with certain bioactive properties has shown therapeutic and preventive effects on these pathologies. This includes the cruciferous vegetable derivative phenylethyl isothiocyanate (PEITC), a bioactive compound present in some vegetables, such as watercress. Notably, PEITC has antioxidant, anti-inflammatory, bactericidal, and anticarcinogenic properties. This review summarized the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discussed the safe and recommended dose of PEITC. In addition, we established a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural molecule for industrial use. With PEITC, there is great potential to develop a viable strategy for preventing cancer and other associated diseases of the gastrointestinal tract. However, this topic still needs more scientific studies to help develop new PEITC products for the nutraceutical, pharmaceutical, or food industries.
... Pre-clinical studies suggest that cruciferous vegetables may also protect against bladder cancer. Specifically, cruciferous vegetables are rich in isothiocyanates, compounds that have been shown to have anticarcinogenic effects against bladder cancer in animal models and in vitro studies [9][10][11][12][13][14][15]. Pre-clinical studies utilizing isothiocyanate in rat bladder cancer models demonstrated inhibition of bladder cancer development and progression [15]. ...
... However, epidemiological studies intended to detect an association between cruciferous vegetable intake and bladder cancer in patients has shown conflicting results. Several small cohort and case control studies have found that cruciferous vegetables are associated with a decreased risk for bladder cancer [9,19,20], while others studies have found no association [9,21,22]. However, these studies were limited by relatively small sample sizes, thus lacking statistical power to detect an association between cruciferous vegetable consumption and bladder cancer risk. ...
... However, epidemiological studies intended to detect an association between cruciferous vegetable intake and bladder cancer in patients has shown conflicting results. Several small cohort and case control studies have found that cruciferous vegetables are associated with a decreased risk for bladder cancer [9,19,20], while others studies have found no association [9,21,22]. However, these studies were limited by relatively small sample sizes, thus lacking statistical power to detect an association between cruciferous vegetable consumption and bladder cancer risk. ...
Article
Background: Abundant pre-clinical data suggest that consumption of cruciferous vegetables might protect against bladder cancer. While small-scale clinical evidence supports this hypothesis, population-level data is lacking. We tested the hypothesis that consumption of cruciferous vegetables is associated with a lower risk of bladder cancer in a large population-based study. Methods: We investigated the association between dietary consumption of cruciferous vegetables and the risk of bladder cancer in the NIH-American Association of Retired Persons (AARP) Diet and Health Study. Diet at baseline was collected with self-administered food-frequency questionnaires. Bladder cancer diagnoses were identified through linkage with state cancer registries. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models. Results: Our analysis included 515,628 individuals. Higher intake of cruciferous vegetables, both overall and when stratified by variety (broccoli vs. brussels sprouts vs. cauliflower), were not associated with bladder cancer risk for men or women. A history of smoking did not affect the results. Conclusions: Our study shows no association between dietary consumption of cruciferous vegetables and incident bladder cancer.
... DaC was expressed as the sum of antioxidant capacity from all foods ingested in a habitual diet (mmol/day). The antioxidant capacity (aC) from foods groups, was also evaluated (mmol/day), using the Food Guide for Brazilian Population [21] as reference for the division into groups: whole cereals, legumes, tubers and roots, total fruits, and total vegetables; additionally, considering the main antioxidant present in food, they were also grouped as follows: cruciferous vegetables, rich in isothiocyanates [22]; orange and dark green vegetables and fruits, rich in beta-carotene [21]; citric foods, rich in Vitamin C [21]; red vegetables and fruits, rich in lycopene [23]; and polyphenol-rich foods and beverages [24,25]. ...
... The FFQ data were transformed into quantitative nutrient information [29] using Microsoft Excel16.0 ® software, based on the Brazilian Food Composition Database [21] and the Food Composition Database of the United States Department of Agriculture [22]. After this data transformation, the quantitative data were grouped into 12 components to evaluate diet quality through BHEI-R [26,27]: total fruits (including fruits and natural fruit juices); whole fruits; total vegetables; dark green and orange vegetables, and legumes; total grains (including grains, roots, and tubers); whole grains; milk and dairy products (including soy drinks); meat, eggs and legumes; oils (including mono and polyunsaturated fats, nuts, seeds, and fish oils); saturated fats; sodium; and calories from solid fats, alcohol and added sugars-SoFAAS. ...
Article
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Food aversions in women undergoing adjuvant chemotherapy for breast cancer may be linked to oxidative stress and gastrointestinal consequences underlying it, and diet possibly plays a role in this association. This follow-up study included 73 women with breast cancer treated in Florianopolis City, Brazil. Dietary antioxidant capacity–DaC (mmol/d), diet quality–Brazilian Healthy Eating Index Revised (BHEI-R score), and oxidative stress biomarkers were accessed before the treatment, and women were asked if they developed food aversions during adjuvant chemotherapy. Red meat was the main aversion-causing food reported (37.9%, n = 9). There was no difference in DaC, BHEI-R score, or oxidative stress biomarkers between women with no food aversion occurrence and those showing food aversions. A logistic regression adjusted model showed that women exhibiting higher BHEI-R scores were 1.08 times more likely to not develop food aversions during adjuvant chemotherapy (p = 0.041). In summary, this innovative investigation showed that diet quality before adjuvant chemotherapy may influence the non-occurrence of food aversion. Considering this, the result opens new areas for early nutritional interventions, focusing on reducing the occurrence of food aversions and consequently benefiting women with breast cancer by having better outcomes in oncologic treatment.
... Cruciferous vegetables, such as cauliflower, cabbage, and broccoli, are the main source of these secondary metabolites capable of mediating different biological processes including oxidative stress and detoxification. Many of these compounds display anticancer properties, and studies have been conducted to investigate their preventive and therapeutic potentials against a variety of cancers (7)(8)(9). Sulforaphane (SFN) is an ITC found in its inactive storage form as glucoraphanin, and its major source is broccoli, an important plant from the family Brassicaceae. Upon mechanical damage (e.g., biting, chewing, or slicing) of broccoli and other cruciferous vegetables, glucoraphanin is released and hydrolyzed by the plant enzyme myrosinase, forming its active molecule SFN ( Figure 1B). ...
Article
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Cancer is a major public health concern worldwide responsible for high morbidity and mortality rates. Alternative therapies have been extensively investigated, and plant-derived compounds have caught the attention of the scientific community due to their chemopreventive and anticancer effects. Sulforaphane (SFN) is one of these naturally occurring agents, and studies have shown that it is able to target a specific cancer cell population displaying stem-like properties, known as cancer stem cells (CSCs). These cells can self-renewal and differentiate to form highly heterogeneous tumor masses. Notably, most of the conventional chemotherapeutic agents cannot target CSCs once they usually exist in a quiescent state and overall, the available cytotoxic drugs focus on highly dividing cells. This is, at least in part, one of the reasons why some oncologic patients relapse after standard therapy. In this review we bring together studies supporting not only the chemopreventive and anticancer properties of SFN, but especially the emerging anti-CSCs effects of this natural product and its potential to be used with conventional antineoplastic drugs in the clinical setting.
... Many studies have shown ITCs to be potent inhibitors of tumorigenesis both in vitro and in vivo. Early investigations have demonstrated that ITCs can inhibit phase I carcinogen-activating enzymes, induce phase II detoxification enzymes, induce cell cycle arrest, induce apoptosis (and autophagy), inhibit angiogenesis, invasion and metastasis [2][3][4][5]. ...
Article
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Diet plays an important role in health. A high intake of plant chemicals such as glucosinolates/isothiocyanates can promote optimal health and decrease the risk of cancer. Recent research has discovered more novel mechanisms of action for the effects of isothiocyanates including the modulation of tumor microenvironment, the inhibition of the self-renewal of stem cells, the rearrangement of multiple pathways of energy metabolism, the modulation of microbiota, and protection against Helicobacter pylori. However, the hormetic/biphasic effects of isothiocyanates may make the recommendations complicated. Isothiocyanates possess potent anti-cancer activities based on up-to-date evidence from in vitro and in vivo studies. The nature of hormesis suggests that the benefits or risks of isothiocyanates largely depend on the dose and endpoint of interest. Isothiocyanates are a promising class of cancer-preventative phytochemicals, but researchers should be aware of the potential adverse (and hormetic) effects. In the authors’ opinion, dietary isothiocyanates are better used as adjunctive treatments in combination with known anti-cancer drugs. The application of nano-formulations and the delivery of isothiocyanates are also discussed in this review.
... Chemoprevention of cancer with natural phytochemical constituents is a revolutionary technique for stopping, or curing cancer 7 . In several years have been seeing that high consuming of Brassicaceae vegetables minimize the risk of a large number of cancers, like lung 8 , gastrointestinal tract 9,10 , prostate 11 and bladder cancers [12][13][14] . The aim of this study was evaluation of the effect of Brassica nigra seeds extract against hepatocellular proliferation induced by phenobarbital, as tumor-promoting agent. ...
Article
Full-text available
Efecto del extracto de semillas de Brassica nigra contra la proliferación hepatocelular inducida por fenobarbital como agente promotor de tumors Abstract DOI:http://doi.org/10.5281/zenodo.7348884 extract against hepatocellular proliferation induced by phenobarbital as tumor promoter agent Hepatocellular proliferation is one of the leading causes of hepatocellular carcinoma (HCC), and is a widely distributed type of cancer-related death. There are considerable challenges in treating hepatocellular carcinoma, including ineffec-tiveness, adverse effects, and drug resistance to available drugs. It has been established that a high intake of Brassica vegetables is linked to a lower risk of many cancers. In the study, Brassica nigra seeds were extracted; phytochemical analysis of the extract was done, including phytochemical screening tests and Gas chromatography-mass spectrometry (GC-MS) analysis. Antiproliferative activity of hydroalcoholic Brassica seeds extract has been studied at 800mg/kg and compared with the control group (given normal saline), phe-nobarbital group (Phenobarbital 75mg/kg), and combination group (Brassica extract 800mg/kg+ Phenobarbital 75mg/kg). The GC-MS analysis revealed the presence of the isothio-cyanate compound. Compared to the phenobarbital group, Combining groups pretreated with Brassica nigra seeds for 14 days and phenobarbital for seven days caused a significant reduction in Ki67 and Bcl2 expression that was obvious in immunohistochemical slides. Also, combination groups showed a substantial decrease in the expression level of genes related to the cell cycle, including minichromosome maintenance genes 2 (Mcm2) and cyclin A2 (Ccna2), and a significant reduction in the expression level of Cytochrome P450, including CYP2B10 and CYP2C29 in comparison with phenobarbital group. Brassica nigra seeds extract showed antiproliferative and apoptotic effects on the liver tissue, suggesting it has a beneficial impact on minimizing the risk of liver cancer. La proliferación hepatocelular es una de las principales cau-sas de carcinoma hepatocelular (HCC) y es un tipo de muerte relacionada con el cáncer ampliamente distribuido. Existen desafíos considerables en el tratamiento del carcinoma he-patocelular, incluida la ineficacia, los efectos adversos y la re-sistencia a los medicamentos disponibles. Se ha establecido que un alto consumo de vegetales Brassica está relacionado con un menor riesgo de muchos tipos de cáncer. En el es-tudio se extrajeron semillas de Brassica nigra; Se realizó un análisis fitoquímico del extracto, incluidas pruebas de selec-ción fitoquímica y análisis de cromatografía de gases-espe-ctrometría de masas (GC-MS). La actividad antiproliferativa del extracto hidroalcohólico de semillas de Brassica se es-tudió a 800 mg/kg y se comparó con el grupo de control (ad-ministrado con solución salina normal), el grupo de fenobar-bital (fenobarbital 75 mg/kg) y el grupo combinado (extracto de Brassica 800 mg/kg + fenobarbital 75 mg/kg). El análisis GC-MS reveló la presencia del compuesto de isotiocianato. En comparación con el grupo de fenobarbital, la combinación de grupos pretratados con semillas de Brassica nigra du-rante 14 días y fenobarbital durante siete días provocó una reducción significativa en la expresión de Ki67 y Bcl2 que fue evidente en los portaobjetos inmunohistoquímicos. Además, los grupos de combinación mostraron una disminución sus-tancial en el nivel de expresión de genes relacionados con el ciclo celular, incluidos los genes de mantenimiento de mini-cromosomas 2 (Mcm2) y ciclina A2 (Ccna2), y una reducción significativa en el nivel de expresión de Citocromo P450, in-cluidos CYP2B10 y CYP2C29 en comparación con el grupo fenobarbital. El extracto de semillas de Brassica nigra mostró efectos antiproliferativos y apoptóticos en el tejido hepático, lo que sugiere que tiene un impacto beneficioso para minimi-zar el riesgo de cáncer de hígado.
... Chemoprevention of cancer with natural phytochemical constituents is a revolutionary technique for stopping, or curing cancer 7 . In several years have been seeing that high consuming of Brassicaceae vegetables minimize the risk of a large number of cancers, like lung 8 , gastrointestinal tract 9,10 , prostate 11 and bladder cancers [12][13][14] . The aim of this study was evaluation of the effect of Brassica nigra seeds extract against hepatocellular proliferation induced by phenobarbital, as tumor-promoting agent. ...
Article
Full-text available
Efecto del extracto de semillas de Brassica nigra contra la proliferación hepatocelular inducida por fenobarbital como agente promotor de tumors Abstract DOI:http://doi.org/10.5281/zenodo.7348884 extract against hepatocellular proliferation induced by phenobarbital as tumor promoter agent Hepatocellular proliferation is one of the leading causes of hepatocellular carcinoma (HCC), and is a widely distributed type of cancer-related death. There are considerable challenges in treating hepatocellular carcinoma, including ineffec-tiveness, adverse effects, and drug resistance to available drugs. It has been established that a high intake of Brassica vegetables is linked to a lower risk of many cancers. In the study, Brassica nigra seeds were extracted; phytochemical analysis of the extract was done, including phytochemical screening tests and Gas chromatography-mass spectrometry (GC-MS) analysis. Antiproliferative activity of hydroalcoholic Brassica seeds extract has been studied at 800mg/kg and compared with the control group (given normal saline), phe-nobarbital group (Phenobarbital 75mg/kg), and combination group (Brassica extract 800mg/kg+ Phenobarbital 75mg/kg). The GC-MS analysis revealed the presence of the isothio-cyanate compound. Compared to the phenobarbital group, Combining groups pretreated with Brassica nigra seeds for 14 days and phenobarbital for seven days caused a significant reduction in Ki67 and Bcl2 expression that was obvious in immunohistochemical slides. Also, combination groups showed a substantial decrease in the expression level of genes related to the cell cycle, including minichromosome maintenance genes 2 (Mcm2) and cyclin A2 (Ccna2), and a significant reduction in the expression level of Cytochrome P450, including CYP2B10 and CYP2C29 in comparison with phenobarbital group. Brassica nigra seeds extract showed antiproliferative and apoptotic effects on the liver tissue, suggesting it has a beneficial impact on minimizing the risk of liver cancer. La proliferación hepatocelular es una de las principales cau-sas de carcinoma hepatocelular (HCC) y es un tipo de muerte relacionada con el cáncer ampliamente distribuido. Existen desafíos considerables en el tratamiento del carcinoma he-patocelular, incluida la ineficacia, los efectos adversos y la re-sistencia a los medicamentos disponibles. Se ha establecido que un alto consumo de vegetales Brassica está relacionado con un menor riesgo de muchos tipos de cáncer. En el es-tudio se extrajeron semillas de Brassica nigra; Se realizó un análisis fitoquímico del extracto, incluidas pruebas de selec-ción fitoquímica y análisis de cromatografía de gases-espe-ctrometría de masas (GC-MS). La actividad antiproliferativa del extracto hidroalcohólico de semillas de Brassica se es-tudió a 800 mg/kg y se comparó con el grupo de control (ad-ministrado con solución salina normal), el grupo de fenobar-bital (fenobarbital 75 mg/kg) y el grupo combinado (extracto de Brassica 800 mg/kg + fenobarbital 75 mg/kg). El análisis GC-MS reveló la presencia del compuesto de isotiocianato. En comparación con el grupo de fenobarbital, la combinación de grupos pretratados con semillas de Brassica nigra du-rante 14 días y fenobarbital durante siete días provocó una reducción significativa en la expresión de Ki67 y Bcl2 que fue evidente en los portaobjetos inmunohistoquímicos. Además, los grupos de combinación mostraron una disminución sus-tancial en el nivel de expresión de genes relacionados con el ciclo celular, incluidos los genes de mantenimiento de mini-cromosomas 2 (Mcm2) y ciclina A2 (Ccna2), y una reducción significativa en el nivel de expresión de Citocromo P450, in-cluidos CYP2B10 y CYP2C29 en comparación con el grupo fenobarbital. El extracto de semillas de Brassica nigra mostró efectos antiproliferativos y apoptóticos en el tejido hepático, lo que sugiere que tiene un impacto beneficioso para minimi-zar el riesgo de cáncer de hígado.
... Upon tissue disruption, for example, by mastication, these sulphurand nitrogen-containing compounds enzymatically hydrolyse into several reactive products, such as isothiocyanates, which are linked to biological activities such as being antiinflammatory [4] or antitumoral [5]. The biological activities of GSL-derived products would, therefore, contribute to the link established between the consumption of cruciferous foods and a lower risk of disease [6], thus reinforcing the dietary importance of these vegetables. Furthermore, these compounds also determine the pungent and bitter flavours that are characteristic of these vegetables [7], so their abundance clearly influences their acceptance. ...
Article
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This work studies the enhancement of glucosinolates (GSLs) in mustard sprouts as health promoters. Sprouts of Sinapis alba, Brassica nigra, and B. carinata were grown under broad-spectrum, monochromatic blue or red light-emitting diode (LED) lamps, irrigated with 0–100 mM sodium chloride (NaCl), and sprayed with 0–250 µM methyl jasmonate (MeJA) as elicitor. The use of LEDs did not result in increased sprout biomass in any case. The effect of the applied treatments on the GSLs depended on the species and were restricted to Brassica spp. The red LEDs produced an overall increase in GSLs over 500% in B. carinata (from 12 to 81 mg 100 g−1 F.W.), compared to the white broad-spectrum lights, although the highest increase in content was obtained in treated sprouts with 250 µM MeJA (104 an 105 mg 101 g−1 F.W., under the red and blue LEDs, respectively). The combination of blue LEDs, 100 mM NaCl, and 250 µM MeJA enhanced the levels of GLSs in B. nigra to the maximum (81 mg 100 g−1 F.W.). Overall, these results indicate that by modifying the growing conditions for a given sprout, enhancement in the accumulation of GSLs as health promoters is possible. The use of these treatments is a sustainable alternative to genetic modification when looking for bioactive-enriched foods, delivering natural plant foods rich in bioactive ingredients (e.g., glucosinolates). Nevertheless, the response to the treatments varies among species, indicating that treatments will require adjustment across sprouts. Further research continues with producing cruciferous sprouts to obtain GSL-enriched formulas for further studying the effects of their bioavailability and bioactivity on health-promotion.
... Since ancient time plants based products and drinks have been used globally for different purposes. Leafy vegetables based products have beneficial effects in treating many human ailments [18][19][20] . These have high content of secondary metabolites with extra nutritional effects 21 . ...
Article
Radish (Raphanus Sativus) used against many toxicants as a natural drug, is a worldwide grown cruciferous root crop with root part the main edible organ and leave part, which in dried form are effective as functional foods. Radish (Raphanus Sativus) that exhibits variety of colors has rich content of vitamins, phenolic compounds, dietary fiber and Phyto-anthocyanin. Based on physico-chemical, nutritional, antioxidant and microbiological properties radish leaves are more nutritionally rich than roots. Leaves are premier source of phenol, flavonoid and have free radical hunting ability. The antioxidant biomarker compound Rutin has been identified only in radish leaves. Therefore the inclusion of Radish leaves in the human diet could have higher bioactive compounds especially flavonoid availability than roots. Conclusion: Consumption of radish leaves mostly discarded may present nutritional and medicinal value to human health especially due to their Antioxidant Activity. Moreover to develop novel functional products more exploration is required to approximate other bioactive compounds from the radish leaves. Keywords: Radish (Raphanus Sativus), bioactive compounds Antioxidants and Skin
... The Brassicaceae family is also characterized by the presence of glucosinolates [13,16]. Many studies have been carried out about glucosinolates and their enzymatically hydrolyzed products (isothiocyanates) for their health-promoting properties and therapeutic benefits [17] such as anti-cancerogenic [18][19][20][21][22], anti-inflammatory [23], as well as anti-diabetogenic [24,25] effects. ...
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The impact of mild oven treatments (steaming or sous vide) and boiling at 10 min, 25 min, or 40 min on health-promoting phytochemicals of orange and violet cauliflower (Brassica oleracea L. var. botrytis) was investigated. For this purpose, targeted ultra-high performance liquid chro-matography-high resolution mass spectrometry analysis of phenolics and glycosylates com-bined with chemometrics was employed. Regardless of cooking time, clear differentiation of cooked samples obtained using different procedures was achieved, thus demonstrating the dis-tinct impact of cooking approaches on sample phytochemical profile (both, compound distribu-tion and content). The main responsible components for the observed discrimination were de-rivatives of hydroxycinnamic acid and kaempferol, organic acids, indolic and aromatic glucos-inolates, with glucosativin that was found, for the first time, as discriminant chemical descriptor in colored cauliflower submitted to steaming and sous-vide. The obtained findings also high-lighted a strict relationship between the impact of the cooking technique used and the type of cauliflower. The boiling process significantly affected phytochemicals in violet cauliflowers whereas orange cauliflower boiled samples were grouped between raw and either steamed or sous-vide cooked samples. Finally, the results confirm that the proposed methodology is capa-ble of discriminating cauliflower samples based on their phytochemical profiles and of identi-fying the cooking procedure able to preserve bioactive constituents.
... This response element is activated when nuclear transcription factor erythroid 2-related factor2 (NRF2) is released from cytosole and translocated to nucleus where it dimerizes with small Maf transcription factor and attaches to these ARE (antioxidant response element) for the initiation of transcription process of phase II enzymes. 88 For instance, SFN is known to be a potent activator of phase II enzymes, inducer of breaks in DNA double strands thereby promoting cellular death, and inducer of caspase mediated apoptosis in bladder and prostate cancer cells. It is also responsible for the over expression of bax & down regulation of Bcl2. ...
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Isothiocyanates are the highly reactive organo-sulphur phytochemicals and are product of hydrolysis of glucosinolates which are present mainly in the cruciferous vegetables. These compounds due to their unique chemical reactivity possess anti-cancer, anti-inflammatory, and neuroprotective properties. Epidemiological and experimental evidences suggest that isothiocyanates reduce oxidative stress and act as indirect antioxidants as well as antimicrobials, therefore, have received attention from the researchers for their possible application in pharmacological and food industry. However, due to high volatility and heat sensitivity of these bioactive compounds, their extraction is very challenging and requires the application of various innovative technologies. In addition to that, their fate during the processing conditions also needs to be considered as these processes tend to affect their bioavailability. Isothiocyanates exhibit wide range of antimicrobial activity due to their ability of reducing oxygen consumption and depolarizing the mitochondrial membrane in bacterial cells. They are generally regarded as safe (GRAS) compounds and hence are allowed to be added to the food as preservatives. Due to their antimicrobial properties, isothiocyanates incorporated food packaging films have become popular in the last decade. They are known to act as substrates to activate lactoperoxidases (LPO) for extension of shelf life of dairy products due to its bactericidal and bacteriostatic properties. This review addresses the detailed evidences supporting the biological activities, bioavailability and stability, methods of extraction, and explanation for their taste perception, as well as utilization of these isothiocyanates in food packaging as natural antimicrobials or natural preservatives to improve shelf life of foodstuffs.
... Glucosinolates are responsible for their spicy taste and pungent odor (25). These compounds are water-soluble anions with the basic structure consisting of a β-D-glucopyranose moiety and β-thioglucoside N-hydroxysulfate with a variable side chain derived from amino acids (26). The glucosinolates are biosynthesized in brassica plants by major three steps of naturally occurring chemical reactions namely, side chain modification, side chain elongation and glucone biosynthesis (8). ...
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In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the “guardian of the genome,” the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. This review discusses the functional foods bioactive compounds derived from several cruciferous vegetables and their use in altering the tumor-suppressive effect of p53 proteins. The association between the mutation of p53 and the incidence of gastrointestinal malignancies (gastric, small intestine, colon, liver, and pancreatic cancers) is also discussed. This review contains crucial information about the use of cruciferous vegetables in the treatment of gastrointestinal tract malignancies.
... Glucosinolates are responsible for their spicy taste and pungent odor (25). These compounds are water-soluble anions with the basic structure consisting of a β-D-glucopyranose moiety and β-thioglucoside N-hydroxysulfate with a variable side chain derived from amino acids (26). The glucosinolates are biosynthesized in brassica plants by major three steps of naturally occurring chemical reactions namely, side chain modification, side chain elongation and glucone biosynthesis (8). ...
Article
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In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the “guardian of the genome,” the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. This review discusses the functional foods bioactive compounds derived from several cruciferous vegetables and their use in altering the tumor-suppressive effect of p53 proteins. The association between the mutation of p53 and the incidence of gastrointestinal malignancies (gastric, small intestine, colon, liver, and pancreatic cancers) is also discussed. This review contains crucial information about the use of cruciferous vegetables in the treatment of gastrointestinal tract malignancies.
... Foods that increase the bioavailable content of non-heme iron and alternative treatments for cancer patients can all benefit from fresh cabbage juice, whether made individually or combined with other vegetables like carrot and celery (61,62) Thiocynate obtained from the hydrolysis of Brassica oleraceae has anticancer and antioxidant properties (60,63). Cauliflower and cruciform vegetable intake has reduced cancer rates (64). Radish sprouts may have a more substantial chemoprotective effect against carcinogens than broccoli sprouts (65). ...
... capitata L. contain large amounts of glucosinolates and these chemicals are broken down to from biologically active molecules during digestion [28]. The potential anti-cancer effects of Cruciferous plants and their derived active components have been already reported [29][30][31]. As the most well-known breakdown products, DIM has been widely studied as an efficient chemoprevention against a range of cancers including melanoma, breast, prostate and colorectal cancers, mostly prompted by its ability to affect tumor cells, including anti-proliferation, apoptosis induction, etc. [32,33]. ...
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Background: Immune checkpoint inhibitors that target programmed cell death protein 1 (PD-1) have obtained encouraging results, but a fraction of tumor patients failed to respond to anti-PD-1 treatment due to the existence of multiple immune suppressive elements such as myeloid-derived suppressor cells (MDSCs). Traditional Chinese medicine or natural products from medicinal plants could enhance immunity and may be helpful for cancer immunotherapy. As a digestive metabolite from cruciferous plants, 3,3'-diindolylmethane (DIM) has been widely used in chemotherapy, but its influence on cancer immunotherapy remains unclear. Here we investigate the function of DIM on MDSCs and examine the therapeutic effects of DIM in conjunction with PD-1 antibody against mouse tumors. Methods: Flow cytometry analysis, Western blot analysis and qRT-PCR assay were used to examine the inhibitory effects and mechanisms of DIM on MDSCs in vitro and in vivo. The therapeutic effects of DIM on cancer immunotherapy by PD-1 antibody were evaluated in mouse models of breast cancer and melanoma tumor. Results: DIM exerted the inhibitory effect on MDSCs via downregulating miR-21 level and subsequently activating PTEN/PIAS3-STAT3 pathways. Adoptive transfer of MDSCs impaired the therapeutic effects of DIM, indicating that the antitumor activity of DIM might be due to the suppression of MDSCs. Furthermore, in mouse models of breast cancer and melanoma tumor, the addition of DIM can enhance the therapeutic effect of PD-1 antibody through promoting T cells responses, and thereby inhibiting tumor growth. Conclusions: Overall, the strategy based on the combination treatment of anti-PD-1 antibody and DIM may provide a new approach for cancer immunotherapy. Cruciferae plants-rich diet which contains high amount of DIM precursor may be beneficial for cancer patients that undergo the anti-PD-1 treatment.
... Foods that increase the bioavailable content of non-heme iron and alternative treatments for cancer patients can all benefit from fresh cabbage juice, whether made individually or combined with other vegetables like carrot and celery (61,62) Thiocynate obtained from the hydrolysis of Brassica oleraceae has anticancer and antioxidant properties (60,63). Cauliflower and cruciform vegetable intake has reduced cancer rates (64). Radish sprouts may have a more substantial chemoprotective effect against carcinogens than broccoli sprouts (65). ...
Article
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Cancer is a severe condition characterized by uncontrolled cell division and increasing reported mortality and diagnostic cases. In 2040, an estimated 28.4 million cancer cases are expected to happen globally. In 2020, an estimated 19.3 million new cancer cases (18.1 million excluding non-melanoma skin cancer) had been diagnosed worldwide, with around 10.0 million cancer deaths. Breast cancer cases have increased by 2.26 million, lung cancer by 2.21 million, stomach by 1.089 million, liver by 0.96 million, and colon cancer by 1.93 million. Cancer is becoming more prevalent in Pakistan, with 19 million new cancer cases recorded in 2020. Food adulteration, gutkha, paan, and nutritional deficiencies are major cancer risk factors that interplay with cancer pathogenesis in this country. Government policies and legislation, cancer treatment challenges, and prevention must be revised seriously. This review presents the current cancer epidemiology in Pakistan to better understand cancer basis. It summarizes current cancer risk factors, causes, and the strategies and policies of the country against cancer.
... The Brassicaceae family turn out to be a focus of rising interest because of its potential to lower the chances of various types of cancers especially lung cancer, gastrointestinal and bladder cancer (Abbaoui, et al, 2018;Navarro, et al, 2011). The potential of cruciferous plants to lower the risk of such deadly diseases is attributed to the carotenoids, fibers, vitamin C, and folic acid present in them along with Sulphur-containing secondary metabolites such as glucosinolates, which are also the reason behind their spicy or bitter taste (Ishida, et al, 2014 ...
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A large number of plants possess medicinal properties due to which they are used as therapeutic agents or an active ingredient of a medicinal preparation. A sizeable fraction of the population throughout the world depends on traditional practices to fight against various infections and diseases and nearly all of it involves the use of plant extracts gathered from a vast diversity of plants which may include Herbs, Shrubs, Trees, Climbers or Creepers. In the present work, we have attempted to study different characteristics of Brassica juncea leaves in different solvents including ethanol, methanol and distilled water, to understand its antimicrobial and antioxidant activity. Brassica juncea comes under the family Cruciferae and genus Brassica, is an important Rabi season oilseed crop. Various tests were carried out to estimate phytochemicals like tannins, flavonoids, phenols, alkaloids, glycosides, terpenoids, amino acids, steroids, anthroquinones, and saponins. Methanol extract of plant leaves were came out to be abundant in phenols and flavonoids. The antioxidant activity of B. juncea was determined by DPPH scavenging activity and it is revealed that methanol extract of this plant leaves possess maximum antioxidant activity. Antibacterial potential of plant leaves extracts were determined in vitro by the help of agar well diffusion method against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumonia and Escherichia coli. Results were also compared with control (Piperacillin/Tazobactam). All the extracts of B. juncea leaves showed appreciable antibacterial activity.
... ITCs are metabolized in the liver by the mercapturic acid pathway and thereafter eliminated in the urine being detected after consumption of glucosinolates. From the perspective of elimination it is interesting to note that ITCs are promising chemopreventives for bladder cancer [57] . In other words, routes of metabolism and elimination may be key sites for their biological activity in certain cancers. ...
Article
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Epidemiological evidence has highlighted the association of specific diets and a lower incidence of cancer. Foremost, the Mediterranean diet provides high levels of polyphenolics and a high consumption of healthier fats, e.g., as from olive oil. In the Mediterranean region the consumption of vegetables is elevated providing a class of compounds, the isothiocyanates (ITCs) as found in the cabbage family. The ITCs have raised great interest for their health benefits over the past few decades. Some of the key ITC compounds, sulforaphane, phenethylisothiocyanate and benzyl isothiocyanate, have been studied in vitro and in vivo and the data support their promise for cancer chemoprevention, as anti-tumor agents, and for chemoprotection of normal tissues and organs. Along with other polyphenolic compounds in the diet, in general, they also possess key anti-inflammatory properties thus satisfying the criteria for compounds that could intervene in cancer initiation and progression. In this review we provide a larger overview of the advantages of including ITCs in the diet as food or as supplements and speculate on what could constitute a valuable therapeutic strategy for improving and sustaining good health and countering cancer disease in humans.
... e primary food sources of glucosinolates in humans are cruciferous vegetables including broccoli, cauliflower, cabbage, Chinese cabbage, Brussels sprouts, collard, kale, kohlrabi, and turnips [24]. Although the glucosinolate concentration of these vegetables is variable, it constitutes approximately 1% of their dry weight [40]. Different broccoli extracts and strains can have very different glucosinolate profiles. ...
Article
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The Brassicaceae family, known as cruciferous vegetables, includes many economic species, mainly edible oil plants, vegetable species, spice plants, and feed plants. Cruciferous vegetables are the foods rich in nutritive composition and are also a good source of dietary fiber. Besides, cruciferous vegetables contain various bioactive chemicals known as glucosinolates and S-methyl cysteine sulfoxide, including sulphur-containing cancer-protective chemicals. Numerous studies have reported that daily intake of sulphurous vegetables helps prevent cancer formation and reduces cancer incidence especially in colorectal cancer through various mechanisms. The potential mechanisms of these compounds in preventing cancer in experimental studies are as follows: protecting cells against DNA damage, inactivating carcinogenic substances, showing antiviral and antibacterial effects, triggering apoptosis in cells with disrupted structure, inhibiting tumour cell migration causing metastasis and the development of tumour-feeding vessels (angiogenesis). These beneficial anticancer effects of cruciferous vegetables are generally associated with glucosinolates in their composition and some secondary metabolites as well as other phenolic compounds, seeds oils and dietary fiber in the literature. This review aims to examine to the roles of cruciferous vegetables and their important bioactive metabolites in the prevention and treatment of colorectal cancer.
... These benefits are due to sulforaphane having faster absorption and high bioavailability [81,82], with appropriate plasma and urine (low excretion) concentrations present [83]. ...
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Background: Metabolic syndrome (MetS) has increased worldwide, and since 2012, prevalence of obesity, hypertension, diabetes, and dyslipidemia has increased in Mexico. Objective: To assess the prevalence of MetS, and its relationship with sociodemographic and lifestyle factors among Mexican adults. Methods: Analytical cross-sectional study nationally representative, carried out on Mexican adults (≥20-year-old adults of both sexes; n = 4595). Socioeconomic factors, geographic area, health care coverage and previous medical diagnoses of diabetes and hypertension, and smoking were assessed. Anthropometrics, and triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-chol), creatinine, and glucose plasma levels were measured. The ATP III MetS definition was applied. Results: A MetS prevalence of 44.2% was observed, which was higher in males than females, and increased with age, lower school level, and overweight. Hyperglycemia, hypertriglyceridemia, low HDL-chol, abdominal obesity, and hypertension were higher in people with MetS, and were associated with obesity. Conclusions: The prevalence of MetS in the Mexican adult observed in the ENSADER 2007 was high, and mainly in men than women. Specific associations of MetS with age, scholar level, and body mass index have been found. Obesity and MetS were associated.
... Its beneficial properties are well known; they are mainly connected to the presence of bioactive sulphoraphane isothiocyanate, which is a product of glucoraphanin enzymatic hydrolysis. There are numerous examples of recent research proving bioactive properties of isothiocyanates which suggest that Brassica vegetables should be included in a daily diet [1][2][3]. ...
Article
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The storage of plant samples as well as sample preparation for extraction have a significant impact on the profile of metabolites, however, these factors are often overlooked during experiments on vegetables or fruit. It was hypothesized that parameters such as sample storage (freezing) and sample pre-treatment methods, including the comminution technique or applied enzyme inhibition methods, could significantly influence the extracted volatile metabolome. Significant changes were observed in the volatile profile of broccoli florets frozen in liquid nitrogen at −20 °C. Those differences were mostly related to the concentration of nitriles and aldehydes. Confocal microscopy indicated some tissue deterioration in the case of slow freezing (−20 °C), whereas the structure of tissue, frozen in liquid nitrogen, was practically intact. Myrosinase activity assay proved that the enzyme remains active after freezing. No pH deviation was noted after sample storage - this parameter did not influence the activity of enzymes. Tissue fragmentation and enzyme-inhibition techniques applied prior to the extraction influenced both the qualitative and quantitative composition of the volatile metabolome of broccoli.
... As mild electrophiles, ITCs form adducts by rapidly reacting with some nucleophiles in the food matrix or in vivo, particularly amino acids (e.g., cysteine) (Abbaoui et al. 2018, Lin et al. 2019, Lu et al. 2020. Lin et al. (2019) and Lu et al. (2020) have previously reported that the adducts of ITCs and cysteine underwent intramolecular cyclization followed by slowly releasing raphanusamic acid/organic amine and 2-carbylamino-4,5-dihydrothiazole-4-carboxylic acids (DCAs)/hydrogen sulfide (H 2 S). ...
Article
Dietary organosulfur-containing compounds (DOSCs) in fruits, vegetables, and edible mushrooms may hold the key to the health-promotion benefits of these foods. Yet their action mechanisms are not clear, partially due to their high reactivity, which leads to the formation of complex compounds during postharvest processing. Among postharvest processing methods, thermal treatment is the most common way to process these edible plants rich in DOSCs, which undergo complex degradation pathways with the generation of numerous derivatives over a short time. At low temperatures, DOSCs are biotransformed slowly during fermentation to different metabolites (e.g., thiols, sulfides, peptides), whose distinctive biological activity remains largely unexplored. In this review, we discuss the bioavailability of DOSCs in human digestion before illustrating their potential mechanisms for health promotion related to cardiovascular health, cancer chemoprevention, and anti-inflammatory and antimicrobial activities. In particular, it is interesting that different DOSCs react with glutathione or cysteine, leading to the slow release of hydrogen sulfide (H 2 S), which has broad bioactivity in chronic disease prevention. In addition, DOSCs may interact with protein thiol groups of different protein targets of importance related to inflammation and phase II enzyme upregulation, among other action pathways critical for health promotion. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... For analysis purposes, plant foods were grouped considering the Food Guide for Brazilian Population [44] as follows: whole cereals, legumes, tubers and roots, total fruits, and total vegetables. Regarding the main type of antioxidant, they were grouped as follows: cruciferous vegetables, rich in isothiocyanates [45]; orange and dark green vegetables and fruits, rich in beta-carotene [38]; citric foods, rich in Vitamin C [38]; red vegetables and fruits, rich in lycopene [46]; and polyphenol-rich foods and beverages, rich in polyphenols [47,48]. ...
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Breast cancer (Bca) is the most common type of cancer among women worldwide, and oxidative stress caused by adjuvant treatment may be decreased by antioxidant intake. The aim of this study is to investigate the associations between Dietary antioxidant Capacity (DaC) and oxidation and antioxidant biomarkers in women undergoing adjuvant treatment (AT) for Bca. This prospective study had a sample of 70 women (52.2 ± 10.7 y). DaC (mmol/g) was calculated using nutritional data obtained from a Food Frequency Questionnaire, and blood was collected to measure the oxidation and antioxidant biomarkers at baseline (T0), and after AT (T1). Carbonylated protein levels were inversely associated with DaC at T1 (p = 0.004); women showed an increased risk of having increment on lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and decrement on ferric reducing antioxidant power (FRAP) and reduced glutathione after AT, in response to lowered DaC (p < 0.05). Carbonylated proteins, TBARS and FRAP levels remained stable between the periods for women at the 3rd DaC tertile at T1, differentiating them from those at the 1st tertile, who showed negative changes in these biomarkers (p < 0.04). DaC may be beneficial for women undergoing AT for Bca, since it promoted a reduction in oxidative stress.
... This reaction increases carcinogen secretion or detoxification that consequently decreases carcinogen-DNA interactions [5]. In this scenario, a variety of ITCs can prevent development of many tumor types, such as murine osteosarcoma [6], human mammary gland [7,8], esophagus [9], liver [10], colon [11], and bladder [12] carcinomas. Many studies presented structural diversity of ITCs, and their synthetic analogs have been successfully tested [8,13]. ...
Article
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Isothiocyanates (ITCs) show strong activity against numerous human tumors. Five structurally diverse ITCs were tested in vivo using the zebrafish embryos 6 and 48 h post-fertilization (hpf). The survival rate, hatching time, and gross morphological changes were assessed 24, 48, and 72 h after treatment with all compounds in various doses (1–10 µM). As a result, we selected a phosphonate analog of sulforaphane (P-ITC; 1–3 µM) as a non-toxic treatment for zebrafish embryos, both 6 and 48 hpf. Furthermore, the in vivo anti-cancerogenic studies with selected 3 µM P-ITC were performed using a set of cell lines derived from the brain (U87), cervical (HeLa), and breast (MDA-MB-231) tumors. For the experiment, cells were labeled using red fluorescence dye Dil (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindocarbocyanine, 10 μg/mL) and injected into the hindbrain ventricle, yolk sac region and Cuvier duct of zebrafish embryos. The tumor size measurement after 48 h of treatment demonstrated the significant inhibition of cancer cell growth in all tested cases by P-ITC compared to the non-treated controls. Our studies provided evidence for P-ITC anti-cancerogenic properties with versatile activity against different cancer types. Additionally, P-ITC demonstrated the safety of use in the living organism at various stages of embryogenesis.
... On the other hand, their effects as natural health-promoting compounds are well known and have been extensively studied since the first evidence showing a relationship between the consumption of cruciferous vegetables and a lower risk of developing cancer of the colon (Dinkova-Kostova & Kostov, 2012). This is reflected by a large number of works and reviews considering the effect (clinical or potentially estimated by in vitro and animal models) of cruciferous crops and ITCs in health and disease (e.g., Abbaoui, Christopher, Riedl, Clinton, & Mortazavi, 2018;Novío, Núñez-Iglesias, & Freire-Garabal, 2019; Quirante-Moya, García-Ibañez, Quirante-Moya, Villaño, & Moreno, 2020;Zhang et al., 2011). Among them, sulforaphane is the most relevant as a healthpromoter. ...
Chapter
Glucosinolates are sulfur compounds responsible at least in part of the the characteristic flavor of cruciferous vegetables and condiments. The glucosinolates [and their cognate bioactive forms, the isothiocyanates (ITCs) and indoles] have been studied for decades because of their antimicrobial, anticancer and antiinflammatory bioactivities Eating cruciferous foods is the direct and easiest way for the intake of glucosinolates; it also has the advantage of the coingestion of plant myrosinase enzymes that mediate the hydrolysis of glucosinolates into their bioactive metabolites: ITCs and indoles. However, industrial and cooking processing can negatively affect the stability of glucosinolates and myrosinases. This chapter reviews the effect that conventional processing has on the content of glucosinolates, commonly associated with losses due to thermal degradation. Alternatively, other innovative, nonthermal processing is reviewed as technologies for preserving these compounds and increasing their extractability. Finally, the established methodologies for the extraction and analysis of glucosinolates are discussed, including alternative protocols for assisting such a task.
... alboglabra) is a native Chinese vegetable belonging to the family of Brassicaceae and its edible organ includes tender stems, young leaves and bolting stems which are rich in vitamin C, carotene, calcium, magnesium, potassium, dietary fiber and glucosinolates [1]. Numerous epidemiological studies have demonstrated that the breakdown products of glucosinolates, such as isothiocyanate (ITCs), sulforaphane (SF) and indole-3-carbinol (I3C), are not only helpful to reduce the risk of cardiovascular disease, but also contribute to decreasing the incidence rate of carcinogenesis including breast, prostate, lung and pancreatic cancer [2][3][4]. Furthermore, GLSs and its derivatives have an important role against the invasion of pathogens and herbivores [5,6], and are also responsible for the specific flavor of Brassica plants [7]. ...
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The content and component of glucosinolates in edible stems and leaves of eight Chinese kale varieties from Japan and eight varieties from China were determined by HPLC-MS. Simultaneously, the expression levels of glucosinolate biosynthesis pathway genes from four varieties with high and low total glucosinolate contents were analyzed by the qRT-PCR method. Four types of aliphatic glucosinolates (A-GLSs: GRA, SIN, GNA and GER) and indole glucosinolates (I-GLSs: 4-HGBS, GBS, 4-MGBS and NGBS) were detected in the stems and leaves of 16 varieties, and no aromatic glucosinolates (R-GLSs) were detected. A-GLSs account for more than 80.69% of the total content of total glucosinolates (T-GLSs), in which GNA and GRA are the main components of stems and leaves. Among Japanese varieties, QB1 has higher content of A- and T-GLSs, while that of XLB was lower; however, the corresponding varieties were ZH and DSHH in Chinese varieties. Among the above four varieties, the expression levels of SOT16, CYP83B1, SOT17, CYP83A1 and MAM1 genes were significantly higher in the varieties with higher GLSs; the expression levels of SOT16 and CYP83B1 were consistent with the content of I-GLSs; and SOT17, CYP83A1 and MAM1 expression levels were consistent with A-GLSs content. At the same time, the expression levels of SOT16 and CYP83B1 in the leaves were higher than those in the stems. CYP83A1 and MAM1 genes were less expressed in the leaves than in the stems of lower content varieties. It is speculated that these genes may be the key genes regulating GLS biosynthesis in Chinese kale.
... In addition to these activities, I3C can also alter sex hormone metabolism, playing a role in preventing hormone-sensitive cancers (48,49). Postinitiation, SFN and I3C can help inhibit the growth of tumors by inducing apoptosis and halting cellular proliferation (19,21,24,(50)(51)(52). SFN and 3-3 ′ -diindolylmethane, the acid condensation product of I3C, have also been shown to inhibit enzymes that regulate epigenetics whose dysregulation contributes to cancer development (25,37,53,54). ...
Article
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Robust evidence shows that phytochemicals from cruciferous vegetables, like broccoli, are associated with numerous health benefits. The anti-cancer properties of these foods are attributed to bioactive isothiocyanates (ITCs) and indoles, phytochemicals generated from biological precursor compounds called glucosinolates. ITCs, and particularly sulforaphane (SFN), are of intense interest as they block the initiation, and suppress the progression of cancer, through genetic and epigenetic mechanisms. The efficacy of these compounds is well-demonstrated in cell culture and animal models, however, high levels of inter-individual variation in absorption and excretion of ITCs is a significant barrier to the use of dietary glucosinolates to prevent and treat disease. The source of inter-individual ITC variation has yet to be fully elucidated and the gut microbiome may play a key role. This review highlights evidence that the gut microbiome influences the metabolic fate and activity of ITCs. Human feeding trials have shown inter-individual variations in gut microbiome composition coincides with variations in ITC absorption and excretion, and some bacteria produce ITCs from glucosinolates. Additionally, consumption of cruciferous vegetables can alter the composition of the gut microbiome and shift the physiochemical environment of the gut lumen, influencing the production of phytochemicals. Microbiome and diet induced changes to ITC metabolism may lead to the decrease of cancer fighting phytochemicals such as SFN and increase the production of biologically inert ones like SFN-nitrile. We conclude by offering perspective on the use of novel “omics” technologies to elucidate the interplay of the gut microbiome and ITC formation.
... Fortunately, myrosinase could be removed without affecting plant bioactive compounds, by ablating myrosin cells, which normally contain myrosinase [245]. Dietary glucosinolates cannot be directly assimilated by mammals (including humans), but are hydrolyzed into isothiocyanates and other cyanates [246], and these compounds have a strong anti-cancer ability because they are one of the best substances in vegetables that induce apoptosis [247][248][249][250]. Isocyanates' ability to inhibit and fight against cancer was reported in several studies [237,[251][252][253][254][255][256]. ...
Article
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Brassica napus is a vegetable oil crop, which is commonly known as rapeseed (or canola). Rapeseed is widely used as a source of oil and protein for food and industrial applications, but also as a remedy, and in a field of attraction or as an ornament due to its diverse flower colors. Every part of rapeseed is useful, even the waste, which could be used to feed animals, or recycled. In this review, the usage of rapeseed in these applications is presented, starting with the preparation of oil and protein from the seeds, before their release in the market, to the utilization of natural unprocessed rapeseed. Progress in rapeseed exploitation for food, remedy, energy source, and industrial applications are analyzed to show variability in diverse findings, to provide insights and progressive descriptions of rapeseed usage to other scholars. Moreover, advancements in breeding for rapeseed improvement were described. In the future, strategies could be developed or improved to avoid or to decrease crop losses, but also to grow the interest in seeking enhancements for valuable traits of rapeseed.
... These benefits are due to sulforaphane having faster absorption and high bioavailability [81,82], with appropriate plasma and urine (low excretion) concentrations present [83]. ...
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For the writing of this manuscript, we searched information published from 2000 to 2021, through PubMed, Web of Science, Springer, and Science Direct. Focusing on the effects related to respiratory diseases, in addition to possible direct effects towards SARS-CoV-2, coupled with diabetes. Diabetes is a metabolic disease that is characterized by affecting the function of glucose, in addition to insulin insufficiency. This leads to patients with such pathologies as being at greater risk for developing multiple complications and increase exposure to viruses infections. This is the case of severe acute respiratory disease coronavirus 19 (SARS-CoV-2), which gave rise to coronavirus disease 2019 (COVID-19), declared an international public health emergency in March of 2020 Currently, several strategies have been applied in order to prevent the majority of the consequences of COVID-19, especially in patients with chronic diseases such as diabetes. Among the possible treatment options, we found that the use of phytochemical compounds has exhibited beneficial effects for the prevention and inhibition of infection by SARS-CoV-2, as well as for the improvement of the manifestations of diabetes.
... Cruciferous vegetables are known to prevent colorectal adenoma development due to high content of isothiocyanates [54]. Also, diets rich in broccoli, are associated with lower risk of bladder cancer [55]. Broccoli (Brassica oleracea var. ...
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Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed. The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation. Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.
... At the population level, epidemiological studies have shown an inverse relationship between the incidence of lung, breast, prostate, colon, and bladder cancer and cruciferous vegetable consumption, offering an appealing, cost-effective, non-pharmacological approach to cancer prevention through dietary intervention [24][25][26][27]. In contrast to these findings, human clinical trials examining the efficacy of cruciferous vegetables interventions on cancer prevention targets showed high levels of inter-individual variation in both the absorption and excretion of ITCs, however, the source of this variation is unknown [28]. ...
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Epidemiological evidence associates the consumption of cruciferous vegetables with reduced risk of several cancers, including renal cell carcinoma. Erucin can be generated by in vivo reduction of sulforaphane or by enzymatic hydrolysis of glucoerucin. Contrarily to sulforaphane, only limited studies have addressed the anticancer properties of erucin. This study aims at evaluating the impact of erucin on renal cell biology. The effects of erucin were assessed in 786‐O and Vero‐E6 cells, representative of human renal cancer and non‐ cancer kidney cells, respectively. Erucin induced a concentration‐dependent decrease in cell viability and cell cycle arrest at G2/Mitosis. In Vero‐E6 cells erucin modestly reduced intracellular reactive oxygen species levels while in 786‐O no effects were detected. After erucin treatment, both cell lines revealed altered morphology, with a concentration‐dependent change from an elongated shape towards a smaller round conformation. Moreover, erucin affected cell adhesion and strongly altered the tubulin network structure and specifically microtubule polymerization. These results are in line with the observed decrease in collective and single cell migration and G2/Mitosis arrest. Overall, erucin may have a beneficial impact in reducing the motility of renal cancer cells. Our results contribute to explore possible dietary approaches for secondary/tertiary renal cancer chemoprevention. This article is protected by copyright. All rights reserved
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This special Issue is to create collections of Articles on specific topics. The aim is to build a community of authors and readers to discuss the latest research and develop new ideas and research directions.The articles in this issue are led by Editors who are experts in the subject and oversee the editorial process for papers.This provide a great platform to promote the break through research works.The potentially advanced special issue focussing on biomedical application from branches of life science, Chemistry andPhysics . This special issue is a join collaboration between Dhanalakshimi srinivasan College of Arts & Science for women Autonomous & International journal of Life Science & Pharma Research. This Provide a platform for the researchers to publish their innovative research findings.It was discussed Antibacterial ,Antifungal, Anticancer, Antioxidant and Anticonventional activities..It also included papers on phytochemical screening and pharmaceutical activity of medicinal plants andalso focused on biosynthesis of Nanomaterials and its Biological applications.The papers in this special issue broadly divided into the applications of Microbiology, Biotechnology,Biochemistry ,Chemistry and Physics.
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This special Issue is to create collections of Articles on specific topics. The aim is to build a community of authors and readers to discuss the latest research and develop new ideas and research directions.The articles in this issue are led by Editors who are experts in the subject and oversee the editorial process for papers.This provide a great platform to promote the break through research works.The potentially advanced special issue focussing on biomedical application from branches of life science, Chemistry andPhysics . This special issue is a join collaboration between Dhanalakshimi srinivasan College of Arts & Science for women Autonomous & International journal of Life Science & Pharma Research. This Provide a platform for the researchers to publish their innovative research findings.It was discussed Antibacterial ,Antifungal, Anticancer, Antioxidant and Anticonventional activities..It also included papers on phytochemical screening and pharmaceutical activity of medicinal plants andalso focused on biosynthesis of Nanomaterials and its Biological applications.The papers in this special issue broadly divided into the applications of Microbiology, Biotechnology,Biochemistry ,Chemistry and Physics.
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Chapter
During the years, numerous evidence reported the extraordinary power of nutrition in both prevention and management of several chronic diseases, including metabolic disorders, cardiovascular diseases and cancer. Indeed, epidemiological studies established the existence of strong relationships between the regular consumption of such foods and the risk of disease development, with both positive and negative meanings. In this sense, a particular interest has been focused on the role of nutrition on cancer risk and prevention. Besides the well-established negative impact of high consumption of red meat- or processed meat-based products, several evidence highlighted the preventive effect of fruits and vegetables, or more generally fibre-rich foods, on various types of cancer, mainly colorectal cancer. Among these kinds of foods, cruciferous vegetables gained great interest by the scientific research. More specifically, bioactive compounds contained in cruciferous vegetables, including indole-3-carbinol and isothiocyanates, have been demonstrated to exert a marked anticancer potential. Several studies, indeed, reported that these phytochemicals show a chemo-preventive activity influencing cancer development since the initial phases, acting through various mechanisms. The present chapter aims to summarise the available literature providing the evidence for the use of bioactive compounds from cruciferous vegetables as chemo-protective agents, focusing the attention on the main representative phytochemicals belonging to this group, such as indole-3-carbinol and isothiocyanates. Also, the main putative mechanisms of action and signalling pathways will be presented and discussed.
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Innate immunity, particularly macrophages, is critical for intestinal homeostasis. Sulforaphane, a dietary isothiocyanate from cruciferous vegetables, has been reported to protect against intestinal inflammation. However, the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet. In this study, sulforaphane effectively attenuated dextran sodium sulphate (DSS) induced intestinal inflammation in murine model. Of note, sulforaphane skewed the switching from classically (M1) to alternatively (M2) activated phenotype both in intestinal and bone marrow-derived macrophages (BMDMs). The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide (LPS) plus interferon gamma-γ (IFN-γ) were suppressed by sulforaphane while M2 marker gene expression levels were improved. This resulted in alteration of inflammatory mediators, particularly interleukin-10 (IL-10), both in colon tissues and culture medium of BMDMs. Subsequently, IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling. This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections. Moreover, anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation. Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.
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Sulforaphane belongs to the active class of isothiocyanates capable of delivering various biological benefits for health promotion and disease prevention. This compound is considered vital to curtail numerous metabolic disorders. Various studies have proven its beneficial effects against cancer prevention and its possible utilization as a therapeutic agent in cancer treatment. Understanding the mechanistic pathways and possible interactions at cellular and subcellular levels is key to design and develop cancer therapeutics for humans. In this respect, a number of mechanisms such as modulation of carcinogen metabolism & phase II enzymatic activities, cell cycle arrest, activation of Nrf2, cytotoxic, proapoptotic and apoptotic pathways have been reported to be involved in cancer prevention. This article provides sufficient information by critical analysis to understand the mechanisms involved in cancer prevention attributed to sulforaphane. Furthermore, various clinical studies have also been included for design and development of novel therapies for cancer prevention and cure. Practical applications Diet and dietary components are potential tools to address various lifestyle-related disorders. Due to plenty of environmental and cellular toxicants, the chances of cancer prevalence are quite large which are worsen by adopting unhealthy lifestyles. Cancer can be treated with various therapies but those are acquiring side effects causing the patients to suffer the treatment regime. Nutraceuticals and functional foods provide safer options to prevent or delay the onset of cancer. In this regard, sulforaphane is a pivotal compound to be targeted as a potential agent for cancer treatment both in preventive and therapeutic regimes. This article provides sufficient evidence via discussing the underlying mechanisms of positive effects of sulforaphane to further the research for developing anticancer drugs that will help assuage this lethal morbidity.
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The blood–urine barrier is the tightest and most impermeable barrier in the body and as such represents a problem for intravesical drug delivery applications. Differentiation-dependent low endocytotic rate of urothelial cells has already been noted; however, the differences in endocytosis of normal and cancer urothelial cells have not been exploited yet. Here we analysed the endocytosis of rhodamine B isothiocyanate-labelled polyacrylic acid-coated cobalt ferrite nanoparticles (NPs) in biomimetic urothelial in vitro models, i.e., in highly and partially differentiated normal urothelial cells, and in cancer cells of the papillary and invasive urothelial neoplasm. We demonstrated that NPs enter papillary and invasive urothelial neoplasm cells by ruffling of the plasma membrane and engulfment of NP aggregates by macropinocytotic mechanism. Transmission electron microscopy (TEM) and spectrophotometric analyses showed that the efficacy of NPs delivery into normal urothelial cells and intercellular space is largely restricted, while it is significantly higher in cancer urothelial cells. Moreover, we showed that the quantification of fluorescent NP internalization in cells or tissues based on fluorescence detection could be misleading and overestimated without TEM analysis. Our findings contribute to the understanding of endocytosis-mediated cellular uptake of NPs in cancer urothelial cells and reveal a highly selective mechanism to distinguish cancer and normal urothelial cells.
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The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa. However, other than smoking cessation, there is a paucity of research that systematically examines agents for chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism based approach, the goal of this review is to summarize epidemiological, in vitro, and preclinical studies, including data regarding the safety, bioavailability, and efficacy of agents evaluated for bladder cancer chemoprevention. Based on the available studies, phytochemicals, specifically isothiocyanates such as sulforaphane, present in Brassicaceae or "cruciferous" vegetables in the precursor form of glucoraphanin are: (a) available in standardized formulations; (b) bioavailable- both systemically and in the bladder; (c) observed to be potent inhibitors of BC carcinogenesis through multiple mechanisms; and (d) without toxicities at these doses. Based on available evidence from epidemiological, in vitro, preclinical, and early phase trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane (SFN) represent a promising potential chemopreventitive agent in bladder cancer.
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The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN mitigates the recruitment and/or retention of the soluble fission factor Drp1 to mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials.
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Background: Phytoene is a tomato carotenoid that may contribute to the apparent health benefits of tomato consumption. Although phytoene is a less prominent tomato carotenoid than lycopene, it is a major carotenoid in various human tissues. Phytoene distribution to plasma lipoproteins and tissues differs from lycopene, suggesting the kinetics of phytoene and lycopene differ. Objective: The objective of this study was to characterize the kinetic parameters of phytoene absorption, distribution, and excretion in adults, to better understand why biodistribution of phytoene differs from lycopene. Methods: Four adults (2 males, 2 females) maintained a controlled phytoene diet (1-5 mg/d) for 42 d. On day 14, each consumed 3.2 mg (13)C-phytoene, produced using tomato cell suspension culture technology. Blood samples were collected at 0, 1-15, 17, 21, and 24 h and 2, 3, 4, 7, 10, 14, 17, 21, and 28 d after (13)C-phytoene consumption. Plasma-unlabeled and plasma-labeled phytoene concentrations were determined using ultra-HPLC-quadrupole time-of-flight-mass spectrometry, and data were fit to a 7-compartment carotenoid kinetic model using WinSAAM 3.0.7 software. Results: Subjects were compliant with a controlled phytoene diet, consuming a mean ± SE of 2.5 ± 0.6 mg/d, resulting in a plasma unlabeled phytoene concentration of 71 ± 14 nmol/L. A maximal plasma (13)C-phytoene concentration of 55.6 ± 5.9 nM was achieved 19.8 ± 9.2 h after consumption, and the plasma half-life was 2.3 ± 0.2 d. Compared with previous results for lycopene, phytoene bioavailability was nearly double at 58% ± 19%, the clearance rate from chylomicrons was slower, and the rates of deposition into and utilization by the slow turnover tissue compartment were nearly 3 times greater. Conclusions: Although only differing from lycopene by 4 double bonds, phytoene exhibits markedly different kinetic characteristics in human plasma, providing insight into metabolic processes contributing to phytoene enrichment in plasma and tissues compared with lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.
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Background Current chemotherapies for advanced stage metastatic bladder cancer often result in severe side effects, and most patients become drug resistant over time. Thus, there is a need for more effective therapies with minimal side effects. Objective The acid/base balance in tumor cells is essential for tumor cell functioning. We reasoned that simultaneous targeting of pH homeostasis and survival pathways would improve therapeutic efficacy. We evaluated the effectiveness of targeting pH homeostasis with the carbonic anhydrase inhibitor acetazolamide (AZ) in combination with the survival pathway targeting isothiocyanate sulforaphane (SFN) on the HTB-9 and RT112(H) human bladder tumor cell lines. Materials and Methods We assessed viability, proliferation, and survival in vitro and effect on xenografts in vivo. Results Combination AZ + SFN treatment induced dose-dependent suppression of growth, produced a potent anti-proliferative and anti-clonogenic effect, and induced apoptosis through caspase-3 and PARP activation. The anti-proliferative effect was corroborated by significant reductions in Ki-67, pHH3, cyclin D1, and sustained induction of the cell cycle inhibitors, p21 and p27. Both active p-Akt (Ser473) and p-S6 were significantly downregulated in the AZ + SFN combination treated cells with a concomitant inhibition of Akt kinase activity. The inhibitory effects of the AZ + SFN combination treatment showed similar efficacy as the dual PI3K/mTOR pathway inhibitor NVP-BEZ235, albeit at an expected higher dose. In terms of the effect on the metastatic potential of these bladder cancers, we found downregulated expression of carbonic anhydrase 9 (CA9) concomitant with reductions in both E-cadherin, N-cadherin, and vimentin proteins mitigating the epithelial-to-mesenchymal transition (EMT), suggesting negation of this program. Conclusion We suggest that reductions in these components could be linked with downregulation of the survival mediated Akt pathway and suggested an active role of the Akt pathway in bladder cancer. Altogether, our in vitro and pre-clinical model data support the potential use of an AZ + SFN combination for the treatment of bladder cancer.
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Clinical practice recommends eating ≥2.5 cups of fruits and vegetables (FVs) each day for cancer prevention, in which the evidence from epidemiological studies for the association between FVs intake and bladder cancer (BC) prevention is inconsistent.We searched the PubMed, Embase, and Willy online Library for relevant studies published up to September 27, 2014. Prospective cohort studies investigated FVs intake, and the risk of BC with ≥3 categories of exposure was included. A dose-response meta-analysis was carried out to evaluate the association between FVs intake and risk of BC.Fourteen cohorts with 17 studies including 9447 cases were identified. No evidence of nonlinear association was examined between FVs intake and risk of BC. The summarized relevant risk (RR) of every 0.2 serving increment a day was 1.00 (95%CI: 0.99, 1.00; P = 0.17; I = 41.7%; n = 14) for total fruits; 0.99 (95%CI: 0.96, 1.01; P = 0.28; I = 37.0%; n = 13) for total vegetables; and 0.99 (95%CI: 0.97, 1.01; P = 0.24; I = 57.5%; n = 8) for both FVs. In further analysis, we observed inverse association between every 0.2 serving increment of green leafy vegetables intake a day and risk of BC (RR = 0.98, 95%CI: 0.96, 0.99; I = 0.0%; P < 0.01; Power = 0.76; n = 6), but neither for cruciferous vegetables (RR = 0.97, 95%CI: 0.93, 1.01; P = 0.19; I = 55.8%; n = 8) nor for citrus (RR = 1.00, 95%CI: 1.00, 1.00; P = 0.83; I = 0.0%; n = 7). Subgroup analysis showed consistent results.Little evidence supports a beneficial effect for total fruits, vegetables, both FVs, and citrus intake against bladder cancer. Green leafy vegetables may help prevent bladder cancer.
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Approximately 80% of human bladder cancers (BC) are non-muscle invasive when first diagnosed and are usually treated by transurethral tumor resection. But 50-80% of patients experience cancer recurrence. Agents for prevention of primary BC have yet to be identified. Existing prophylactics against BC recurrence, e.g., Bacillus Calmette-Guerin (BCG), have limited efficacy and utility; they engender significant side effects and require urethral catheterization. Many cruciferous vegetables, rich sources of isothiocyanates (ITCs), are commonly consumed by humans. Many ITCs possess promising chemopreventive activities against BC and its recurrence. Moreover, orally ingested ITCs are selectively delivered to bladder via urinary excretion. This review is focused on urinary delivery of ITCs to the bladder, their cellular uptake, their chemopreventive activities in preclinical and epidemiological studies that are particularly relevant to prevention of BC recurrence and progression, and their chemopreventive mechanisms in BC cells and tissues.
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The answer to chemoprevention has perhaps been available to the general public since the dawn of time. The epigenetic diet is of extreme interest, for research suggests that cruciferous vegetables are not only an important source of nutrients, but perhaps a key to eliminating cancer as a life-threatening disease. Cruciferous vegetables such as kale, cabbage, Brussels sprouts, and broccoli sprouts contain chemical components, such as sulforaphane (SFN) and indole-3-carbinol (I3C), which have been revealed to be regulators of microRNAs (miRNAs) and inhibitors of histone deacetylases (HDACs) and DNA methyltransferases (DNMTs). The mis-regulation and overexpression of these genes are responsible for the uncontrolled cellular proliferation and viability of various types of cancer cells. The field of epigenetics and its incorporation into modern medicinal investigation is an exponentially growing field of interest and it is becoming increasingly apparent that the incorporation of an epigenetic diet may in fact be the key to chemoprevention.
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Isothiocyanates (ITCs) from biodegradation of glucosinolates comprise a group of electrophiles associated with growth-inhibitory effects in plant- and mammalian cells. The underlying modes of action of this feature are not fully understood. Clarifying this has involved mammalian cancer cells due to ITCs' chemopreventive potential. The binding of ITCs to tubulins has been reported as a mechanism by which ITCs induce cell cycle arrest and apoptosis. In the present study we demonstrate that ITCs disrupt microtubules in Arabidopsis thaliana contributing to the observed inhibited growth phenotype. We also confirmed this in rat bladder cancer cells (AY-27) suggesting that cells from plant and animals share mechanisms by which ITCs affect growth. Exposure of A. thaliana to vapor-phase of allyl ITC (AITC) inhibited growth and induced a concurrent bleaching of leaves in a dose-dependent manner. Transcriptional analysis was used to show an upregulation of heat shock-genes upon AITC-treatment. Transgenic A. thaliana expressing GFP-marked α-tubulin was employed to show a time- and dose-dependent disintegration of microtubules by AITC. Treatment of AY-27 with ITCs resulted in a time- and dose-dependent decrease of cell proliferation and G2/M-arrest. AY-27 transiently transfected to express GFP-tagged α-tubulin were treated with ITCs resulting in a loss of microtubular filaments and the subsequent formation of apoptotic bodies. In conclusion, our data demonstrate an ITC-induced mechanism leading to growth inhibition in A. thaliana and rat bladder cancer cells, and expose clues to the mechanisms underlying the physiological role of glucosinolates in vivo.
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Smoking is estimated to cause about half of all bladder cancer cases. Case-control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk. As part of the World Cancer Research/American Institute for Cancer Research Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies to assess the dose-response relationship between fruit and vegetables and incidence and mortality of bladder cancer. We searched PubMed up to December 2013 for relevant prospective studies. We conducted highest compared with lowest meta-analyses and dose-response meta-analyses using random effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and used restricted cubic splines to examine possible nonlinear associations. Fifteen prospective studies were included in the review. The summary RR for an increase of 1 serving/day (80 g) were 0.97 (95% CI: 0.95-0.99) I(2) = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94-1.00, I(2) = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96-1.00, I(2) = 0%, 12 studies) for fruits. Results were similar in men and women and in current, former and nonsmokers. Amongst fruits and vegetables subgroups, for citrus fruits the summary RR for the highest compared with the lowest intake was 0.87 (95% CI: 0.76-0.99, I(2) = 0%, eight studies) and for cruciferous vegetables there was evidence of a nonlinear relationship (P = 0.001). The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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Background: Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. Methods: We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Results: Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. Conclusion: This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.
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Dietary lipids have been shown to increase bioavailability of provitamin A carotenoids from a single meal, but the effects of dietary lipids on conversion to vitamin A during absorption are essentially unknown. Based on previous animal studies, we hypothesized that the consumption of provitamin A carotenoids with dietary lipid would enhance conversion to vitamin A during absorption compared with the consumption of provitamin A carotenoids alone. Two separate sets of 12 healthy men and women were recruited for 2 randomized, 2-way crossover studies. One meal was served with fresh avocado (Persea americana Mill), cultivated variety Hass (delivering 23 g of lipid), and a second meal was served without avocado. In study 1, the source of provitamin A carotenoids was a tomato sauce made from a novel, high-β-carotene variety of tomatoes (delivering 33.7 mg of β-carotene). In study 2, the source of provitamin A carotenoids was raw carrots (delivering 27.3 mg of β-carotene and 18.7 mg of α-carotene). Postprandial blood samples were taken over 12 h, and provitamin A carotenoids and vitamin A were quantified in triglyceride-rich lipoprotein fractions to determine baseline-corrected area under the concentration-vs.-time curve. Consumption of lipid-rich avocado enhanced the absorption of β-carotene from study 1 by 2.4-fold (P < 0.0001). In study 2, the absorption of β-carotene and α-carotene increased by 6.6- and 4.8-fold, respectively (P < 0.0001 for both). Most notably, consumption of avocado enhanced the efficiency of conversion to vitamin A (as measured by retinyl esters) by 4.6-fold in study 1 (P < 0.0001) and 12.6-fold in study 2 (P = 0.0013). These observations highlight the importance of provitamin A carotenoid consumption with a lipid-rich food such as avocado for maximum absorption and conversion to vitamin A, especially in populations in which vitamin A deficiency is prevalent. This trial was registered at clinicaltrials.gov as NCT01432210.
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Aims and Background To describe the cancer prevalence in elderly Italian people and analyze the differences, if any, with the prevalence among younger subjects. Methods & Study Design The cancer prevalence among elderly patients (65 years and over), the three age classes encompassing elderly age (65-74 years, 75-84 years, 85 years and over) and younger patients (0-64 years) was computed using the PREVAL method on the basis of the incident cases over the period 1976-1992 followed up to 31 December 1992 (prevalence reference date). Data were collected by 11 Italian cancer registries. Results The observed prevalence figures for all cancers (except skin epitheliomas), both sexes combined and considering the whole elderly group, were 1,090 and 3,601 cases per 100,000 one and five years since diagnosis, respectively; the prevalence increased up to the 75-84 age group and showed a slight decrease after age 85. With regard to specific cancer sites, in men bladder and prostate had the highest prevalence 5 years from diagnosis (more than 800 cases per 100,000), followed by colon and lung (about 500 cases per 100,000) stomach and rectum (about 300 cases per 100,000); in women breast cancer ranked first (more than 1,000 cases per 100,000), followed by colon (about 350 cases per 100,000), corpus uteri, stomach and rectum cancers (between 150 and 200 cases per 100,000). For all malignancies and the two sexes combined the prevalence figures were about six times higher in the older than in the younger age group. Conclusions These figures confirm the important role of aging in determining the increase in cancer prevalence. The resulting prevalence figures clearly indicate the cancer burden placed on health care services; moreover, the figures will probably increase in the next decades due to a possible improvement in survival and to the dramatic aging of the population, assuming a stable trend for incidence rates. This picture will represent a major challenge for politicians and those dealing with health care planning and social policies in general, especially in the light of the reduction of the available financial resources and the specific features of medical and social needs in the elderly.
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Scope: Several lines of evidence suggest that the consumption of cruciferous vegetables is beneficial to human health. Yet, underlying mechanisms and key molecular targets that are involved with achieving these benefits in humans are still not fully understood. To accelerate this research, we conducted a human study to identify potential molecular targets of crucifers for further study. This study aimed to characterize plasma metabolite profiles in humans before and after consuming fresh broccoli sprouts (a rich dietary source of bioactive sulforaphane). Methods and results: Ten healthy adults consumed fresh broccoli sprouts (containing 200 μmol sulforaphane equivalents) at time 0 and provided blood samples at 0, 3, 6, 12, 24 and 48 hours. An untargeted metabolomics screen revealed that levels of several plasma metabolites were significantly different before and after sprout intake, including fatty acids (14:0, 14:1, 16:0, 16:1, 18:0, 18:1), glutathione, glutamine, cysteine, dehydroepiandrosterone, and deoxyuridine monophosphate. Evaluation of all time points was conducted using paired t test (R software) and repeated measures ANOVA for a within-subject design (Progenesis QI). Conclusion: This investigation identified several potential molecular targets of crucifers that may aid in studying established and emerging health benefits of consuming cruciferous vegetables and related bioactive compounds. This article is protected by copyright. All rights reserved.
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Intake of isothiocyanates (ITCs), naturally occurring as hydrolization products from glucosinolates (GLSs) in brassicaceae, has, in epidemiological studies, been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of ITCs, mainly related to a.) detoxification (induction of phase II enzymes), b.) anti-inflammatory properties by down-regulation of NFkappaB activity, c.) cyclin-mediated cell cycle arrest and d.) epigenetic modulation by inhibition of histone deacetylase activity. First prospective clinical trials were promising in patients with risk of prostate cancer recurrence. The glutathione-S-transferase gene expression seems to play a major role in the individual susceptibility towards ITCs. Safety issues are widely unclear and should be more addressed in future studies because ITCs can, in low concentrations, compromise the function of human immune cells and might impair genome stability.
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Brassica originated feed and fodders are the chief source of glucosinolates in animal diets. High intake of glucosinolates induce several health and production problem in animals, however low glucosinolates containing meals may be good source of protein especially of sulfur containing amino acids. Recent research on glucosinolates shown that feeding of low glucosinolates containing meals reduce fungus infestation of ration, increase isothiocynate content of animal produce and increased peripheral fat with higher contents of unsaturated fatty acids (C18:00, 1 trans, C22:2) in carcass and milk fat, are advantages of Brassica meal feeding because isothiocyantes and unsaturated fatty acids exerts anti-carcinogenic properties. The deleterious effects of high glucosinolate containing meals could be eliminated using a suitable detoxification technology and keeping the level of glucosinolate within tolerable limits.
Article
Background: Isothiocyanates derived from the Brassicaceae plants possess chemopreventive and anticancer activities. One of them is sulforaphene (SF), which is abundant in Rhapanus sativus seeds. The underlying mechanism of its anticancer activity is still underexplored. Purpose: SF properties make it an interesting candidate for cancer prevention and therapy. Thus, it is crucial to characterize the mechanism of its activity. Study design: We investigated the mechanism of antiproliferative activity of SF in breast cancer cells differing in growth factor receptors status and lacking functional p53. Methods: Viability of SKBR-3 and MDA-MB-231 breast cancer cells treated with SF was determined by SRB and clonogenic assays. Cell cycle, cell death and oxidative stress were analyzed by flow cytometry or microscopy. The levels of apoptosis and autophagy markers were assessed by immunoblotting. Results: SF efficiently decreased the viability of breast cancer cells, while normal cells (MCF10A) were less sensitive to the analyzed isothiocyanate. SF induced G2/M cell cycle arrest, as well as disturbed cytoskeletal organization and reduced clonogenic potential of the cancer cells. SF induced apoptosis in a concentration-dependent manner which was associated with the oxidative stress, mitochondria dysfunction, increased Bax:Bcl2 ratio and ADRP levels. SF also potentiated autophagy which played a cytoprotective role. Conclusions: SF exhibits cytotoxic activity against breast cancer cells even at relatively low concentrations (5-10µM). This is associated with induction of the cell cycle arrest and apoptosis. SF might be considered as a potent anticancer agent.