stilbenes and sulforaphane

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies.

Topics: Animals; Anticarcinogenic Agents; Antioxidant Response Elements; Antioxidants; Curcumin; Cysteine Proteinase Inhibitors; Diabetic Nephropathies; Enzyme Inhibitors; Humans; Isothiocyanates; Leupeptins; Molecular Targeted Therapy; NF-E2-Related Factor 2; Oxidative Stress; Resveratrol; Rutin; Signal Transduction; Stilbenes; Sulfoxides; Trace Elements; Zinc

Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols (

Topics: Animals; Anthocyanins; Antioxidants; Carotenoids; Catechin; Coumestrol; Curcumin; Energy Metabolism; Fatty Liver; Glucosinolates; Humans; Imidoesters; Isothiocyanates; Lipogenesis; Mitochondria; Non-alcoholic Fatty Liver Disease; Nutritional Sciences; Oxidative Stress; Oximes; Polyphenols; Quercetin; Resveratrol; Stilbenes; Sulfoxides; Xanthophylls

The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements.

Topics: Animals; Anticarcinogenic Agents; Area Under Curve; Brassica; Chemoprevention; Curcumin; Disease Models, Animal; Exercise; Gene Expression Profiling; Glucosinolates; Glycoside Hydrolases; Humans; Isothiocyanates; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Nitriles; Nutrigenomics; Nutritional Sciences; Oxidation-Reduction; Phytochemicals; Resveratrol; Signal Transduction; Silymarin; Stilbenes; Sulfoxides

Diet has been linked to an overwhelming proportion of cancers. Current chemotherapy and targeted therapies are limited by toxicity and the development of resistance against these treatments results in cancer recurrence or progression. In vitro evidence indicates that a number of dietary-derived agents have activity against a highly tumorigenic, chemoradiotherapy resistant population of cells within a tumour. This population is associated with cancer recurrence and is therefore clinically significant. Targeting this subpopulation, termed cancer stem-like cells with dietary-derived agents provides a potentially low toxicity strategy to enhance current treatment regimens. In addition, dietary-derived compounds also provide a novel approach to cancer prevention strategies. This review focusses on selected diet-derived agents that have been shown to specifically target cancer stem-like cells using in vivo models, or in clinical trials. Furthermore, the potential limitations of these studies are discussed, and areas of research that need to be addressed to allow successful translation of dietary-derived agents to the clinical arena are highlighted.

Topics: Animals; Anticarcinogenic Agents; Catechin; Cell Line, Tumor; Curcumin; Diet; Disease Models, Animal; Flavonoids; Humans; Isothiocyanates; Neoplasms; Neoplastic Stem Cells; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes; Sulfoxides; Vitamin A

Hepatocellular carcinoma (HCC) is an aggressive and life-threatening disease often diagnosed at intermediate or advanced stages, which substantially limits therapeutic approaches to its successful treatment. This indicates that the prevention of HCC may be the most promising strategy in reducing its incidence and mortality. Emerging evidence indicates that numerous nutrients and nonnutrient dietary bioactive components can reduce the occurrence and/or delay the development of HCC through modifications of deregulated epigenetic mechanisms. This review examines the existing knowledge on the epigenetic mechanism-based studies in in vitro and in vivo models of HCC on the chemopreventive potential of epigenetic food components, including dietary methyl-group donors, epigallocatechin-3-gallate, sodium butyrate, resveratrol, curcumin, and sulforaphane, on liver carcinogenesis. Future direction and potential challenges in the effective use of bioactive food constituents in the prevention of HCC are highlighted and discussed.

Topics: Animals; Butyric Acid; Carcinoma, Hepatocellular; Catechin; Cell Line, Tumor; Curcumin; Disease Models, Animal; DNA Methylation; Epigenesis, Genetic; Food; Humans; Isothiocyanates; Phytochemicals; Resveratrol; Stilbenes; Sulfoxides

The pathogenesis of neurodegenerative diseases involves altered activity of proteolytic systems and accumulation of protein aggregates. Autophagy is an intracellular process in which damaged organelles and long-lived proteins are degraded and recycled for maintaining normal cellular homeostasis. Disruption of autophagic activity in neurons leads to modify the cellular homeostasis, causing deficient elimination of abnormal and toxic protein aggregates that promotes cellular stress and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons to clear abnormal protein aggregates and survive. This review aims to give an overview of some of the main modulators of autophagy that are currently being studied as possible alternatives in the search of therapies that slow the progression of neurodegenerative diseases, which are incurable to date.

Topics: Animals; Autophagy; Disease Models, Animal; Food; Humans; Isothiocyanates; Lithium; Neurodegenerative Diseases; Resveratrol; Sirolimus; Spermidine; Stilbenes; Sulfoxides; Trehalose; Valproic Acid

Diabetes is increasing at an alarming rate and, despite anti-hypertensive and insulin therapies, diabetic patients are still at risk of developing complications such as chronic kidney disease, cardiovascular disease, and retinopathy. There is therefore an urgent need for more effective therapies to prevent the development and progression of diabetic complications. Oxidative stress is a major player in the aetiology of diabetic complications. However, results from clinical trials thus far using general antioxidants have been disappointing. Mechanism-based antioxidants have gained considerable attention due to their more targeted approach at reducing oxidative stress and associated complications in diabetes. The transcription factor, NFE2-related factor 2 (Nrf2), is a master regulator of redox homeostasis and the cellular detoxification response. Instead of relying on a single antioxidant, activation of Nrf2 results in the concerted upregulation of several antioxidant enzymes and cytoprotective genes, making it an attractive therapeutic target for diabetic complications. Several Nrf2 activators have been discovered and have proven effective at activating Nrf2 signalling through different mechanisms in both in vitro and in vivo models of diabetes. This review will address some of the most promising and well-known Nrf2 activators and their roles in preventing the development and progression of diabetic complications. Challenges facing the advancement of this drug class into the clinic will be discussed, as will be the future of Nrf2 activation as a therapeutic strategy in preventing the development of diabetic complications.

Topics: Animals; Diabetes Complications; Humans; Intracellular Signaling Peptides and Proteins; Isothiocyanates; Kelch-Like ECH-Associated Protein 1; Leupeptins; Mice; Mice, Knockout; Molecular Targeted Therapy; NF-E2-Related Factor 2; Oleanolic Acid; Oxidative Stress; Resveratrol; Stilbenes; Sulfoxides

The pronounced effects of the epigenetic diet (ED) and caloric restriction (CR) have on epigenetic gene regulation have been documented in many pre-clinical and clinical studies. Understanding epigenetics is of high importance because of the concept that external factors such as nutrition and diet may possess the ability to alter gene expression without modifying the DNA sequence. The ED introduces bioactive medicinal chemistry compounds such as sulforaphane (SFN), curcumin (CCM), epigallocatechin gallate (EGCG) and resveratrol (RSV) that are thought to aid in extending the human lifespan. CR, although similar to ED in the target of longevity, mildly reduces the total daily calorie intake while concurrently providing all beneficial nutrients. Both CR and ED may act as epigenetic modifiers to slow the aging process through histone modification, DNA methylation, and by modulating microRNA expression. CR and ED have been proposed as two important mechanisms that modulate and potentially slow the progression of age-related diseases such as cardiovascular disease (CVD), cancer, obesity, Alzheimer's and osteoporosis to name a few. While many investigators have examined CR and ED as separate entities, this review will primarily focus on both as they relate to age-related diseases, their epigenetic effects and their medicinal chemistry.

Topics: Aging; Anticarcinogenic Agents; Caloric Restriction; Catechin; Chemistry, Pharmaceutical; Curcumin; Epigenesis, Genetic; Humans; Isothiocyanates; Resveratrol; Stilbenes; Sulfoxides

Even though conventional cancer therapies, comprising surgery and chemo- and radiotherapy, play an important role in the treatment of most solid tumours, successful therapeutic outcome is often limited due to high toxicity and related side-effects, as well as the development of multi-drug resistances. Therefore, there is need for new therapeutic strategies not only to obtain higher treatment efficacy, but also for the reduction of toxicity and adverse effects. Emerging evidence suggests that natural compounds with distinct anticarcinogenic activity may be considered as potential agents for enhancing the therapeutic effects of common cancer treatments. By using the examples of resveratrol and sulforaphane this review will summarize the findings of recent investigations focusing this topic so far and the current knowledge of the molecular mechanisms by which these selected phytochemicals may potentiate the anti-tumor effects of different cancer therapies.

Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Interactions; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Isothiocyanates; Neoplasms; Resveratrol; Stilbenes; Sulfoxides; Thiocyanates

The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.

Topics: Alkaloids; Animals; Anticarcinogenic Agents; Benzodioxoles; beta Catenin; Carotenoids; Catechin; Cell Differentiation; Cell Proliferation; Cholecalciferol; Curcumin; Diet; Humans; Isoflavones; Isothiocyanates; Lycopene; Neoplasms; Neoplastic Stem Cells; Piperidines; Polyunsaturated Alkamides; Resveratrol; Signal Transduction; Stilbenes; Sulfoxides; Thiocyanates; Wnt Proteins

The correlation between glutamine metabolism and oncogene expression in cancers has led to a renewed interest in the role of glutamine in cancer cell survival. Hyperpolarized [5-(13) C]glutamine is evaluated as a potential biomarker for noninvasive metabolic measurements of drug response in prostate cancer cells.. Hyperpolarized [5-(13) C]glutamine is used to measure glutamine metabolism in two prostate cancer cell lines (PC3 and DU145) before and after treatment with the two natural anticancer drugs resveratrol and sulforaphane. An invasive biochemical assay simulating the hyperpolarized experiment is used to independently quantify glutamine metabolism.. Glutamine metabolism is found to be 4 times higher in the more glutaminolytic DU145 cells compared with PC3 cells under proliferating growth conditions by using hyperpolarized [5-(13) C]glutamine as a noninvasive probe. A significant decrease in glutamine metabolism occurs upon apoptotic response to treatment with resveratrol and sulforaphane.. Hyperpolarized NMR using [5-(13) C]glutamine as a probe permits the noninvasive observation of glutaminolysis in different cell lines and under different treatment conditions. Hyperpolarized [5-(13) C]glutamine metabolism thus is a promising biomarker for the noninvasive detection of tumor response to treatment, as it directly monitors one of the hallmarks in cancer metabolism - glutaminolysis - in living cells.

Topics: Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Biomarkers, Tumor; Carbon Isotopes; Cells, Cultured; Chromatography, High Pressure Liquid; Contrast Media; Enzyme-Linked Immunosorbent Assay; Gadolinium; Glutamine; Heterocyclic Compounds; Humans; In Vitro Techniques; Isothiocyanates; Magnetic Resonance Spectroscopy; Male; Organometallic Compounds; Phenotype; Prostatic Neoplasms; Resveratrol; Stilbenes; Sulfoxides

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is evoked by diverse pathophysiological conditions and/or surgical procedures. Here, we evaluated the nephropreventive effect of sulfotransferase (SULT) inhibitors, quercetin, and resveratrol, which hamper hepatic indoxyl sulfate (IS) production. I/R of the kidney caused severe renal injury with marked accumulation of serum and renal IS and urinary excretion of kidney injury molecule-1. Oral administration of AST-120 resulted in a significant restoration of kidney injury, suggesting that uremic toxins, which can be suppressed or adsorbed by AST-120 in the intestine, contribute to the progression or development of I/R-induced AKI. Oral administration of resveratrol or quercetin, SULT inhibitors, suppressed IS accumulation, accompanied by significant amelioration of renal dysfunction. The expression of nuclear factor E2-related factor 2 (Nrf2) in the renal nuclear fractions was markedly elevated by renal I/R, but suppressed by treatment with SULT inhibitors. IS is primarily taken up by HK-2 cells derived from human proximal tubular cells via organic anion transporters, which then evokes activation of Nrf2, most likely due to intracellular oxidative stress. Renal basolateral organic anion transporters OAT1 and OAT3, which mediate renal tubular uptake of IS in basolateral membrane, were markedly downregulated by renal I/R, but restored by SULT inhibitors. Our results suggest that renal accumulation of IS in ischemic AKI induces oxidative stress and downregulation of organic anion transporters resulting in kidney damage, which could be restored to some extent by inhibiting hepatic SULT activity as a nephropreventive target.

Topics: Acute Kidney Injury; Animals; Blotting, Western; Carbon; Cell Line; Chromatography, High Pressure Liquid; Enzyme Inhibitors; Humans; Indican; Isothiocyanates; Lipid Peroxidation; Liver; Male; NF-E2-Related Factor 2; Oxides; Quercetin; Rats, Sprague-Dawley; Reperfusion Injury; Resveratrol; Stilbenes; Sulfotransferases; Sulfoxides

Epigallocatechin-3-gallate (EGCG), a catechin gallate ester, is the major component of green tea and has been demonstrated to inhibit tumor growth as well as inhibit smooth muscle cell migration. We evaluated the effect of the phytochemicals resveratrol, allicin, sulforaphane (SFN), and EGCG on intimal hyperplasia in the carotid artery injury model.. Intimal hyperplasia was induced in carotid arteries of adult Sprague-Dawley rats with a wire injury. Experimental animals received intraperitoneal injections of one of the four phytochemicals daily beginning 1 day prior to surgery and continued for up to 4 weeks. Control animals were administered saline. Carotid specimens were harvested at 2 weeks and subjected to quantitative image analysis. In addition, EGCG specimens were analyzed for cell proliferation, immunohistochemistry, and Western blot analysis.. Quantitative image analysis showed significant phytochemical suppression of intimal hyperplasia at 2 and 4 weeks postoperatively with EGCG (62% decrease in intimal area). Significant decreases were also noted at 2 weeks for SFN (56%) and resveratrol (44%), whereas the decrease with allicin (24%) was not significant. Quantification of intimal hyperplasia by intima:media ratio showed similar results. Cell proliferation assay of specimens demonstrated suppression by EGCG. Immunohistochemical staining of EGCG-treated specimens showed extracellular signal-regulated kinase (ERK) suppression but not of the c-jun N-terminal kinase or p38 pathways. Western blot analysis confirmed reduced ERK activation in arteries treated with EGCG.. Intraperitoneal injection of the phytochemicals EGCG, SFN, resveratrol, and allicin have suppressive effects on the development of intimal hyperplasia in the carotid artery injury model, with maximal effect due to EGCG. The mechanism of EGCG action may be due to inhibition of ERK activation. EGCG may affect a common pathway underlying either neoplastic cellular growth or vascular smooth muscle cellular proliferation.

Topics: Animals; Cardiovascular Agents; Carotid Artery Injuries; Carotid Artery, Common; Carotid Intima-Media Thickness; Catechin; Cell Proliferation; Disease Models, Animal; Disulfides; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Hyperplasia; Injections, Intraperitoneal; Isothiocyanates; Male; Neointima; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Sulfinic Acids; Sulfoxides; Time Factors

Neurons rely on the release and subsequent cleavage of GSH to cysteinylglycine (CysGly) by astrocytes in order to maintain optimal intracellular GSH levels. In neurodegenerative diseases characterised by oxidative stress, neurons need an optimal GSH supply to defend themselves against free radicals released from activated microglia and astroglia. The rate of GSH synthesis is controlled largely by the activity of γ-glutamyl cysteine ligase. Expression of γ-glutamyl cysteine ligase and of the Xc- system, which facilitates cystine uptake, is regulated by the redox-sensitive transcription factor, nuclear factor erythroid-2-related factor 2 (Nrf2). Compounds that can activate the Nrf2-ARE pathway, referred to as 'Nrf2 activators' are receiving growing attention due to their potential as GSH-boosting drugs. This study compares four known Nrf2 activators, R-α-Lipoic acid (LA), tert-butylhydroquinone (TBHQ), sulforaphane (SFN) and Polygonum cuspidatum extract containing 50% resveratrol (PC-Res) for their effects on astroglial release of GSH and CysGly. GSH levels increased dose-dependently in response to all four drugs. Sulforaphane produced the most potent effect, increasing GSH by up to 2.4-fold. PC-Res increased GSH up to 1.6-fold, followed by TBHQ (1.5-fold) and LA (1.4-fold). GSH is processed by the ectoenzyme, γ-glutamyl transpeptidase, to form CysGly. Once again, SFN produced the most potent effect, increasing CysGly by up to 1.7-fold, compared to control cells. TBHQ and PC-Res both induced fold increases of 1.3, followed by LA with a fold increase of 1.2. The results from the present study showed that sulforaphane, followed by lipoic acid, resveratrol and Polygonum multiflorum were all identified as potent "GSH and Cys-Gly boosters".

Topics: Astrocytes; Cell Line, Tumor; Cell Survival; Dipeptides; Glutathione; Homocysteine; Humans; Hydroquinones; Isothiocyanates; NF-E2-Related Factor 2; Plant Extracts; Resveratrol; Stilbenes; Sulfoxides; Thioctic Acid

Topics: Animals; Brassica; Breeding; Cooking; Curcumin; Diet; Fruit; Genetic Variation; Genistein; Genome, Human; Humans; Isothiocyanates; Metagenome; Mice; Neoplasms; Phytotherapy; Rats; Reproducibility of Results; Resveratrol; Risk Management; Stilbenes; Sulfoxides; Thiocyanates; Time Factors; Vegetables

Resveratrol is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Sulforaphane belongs to the family of isothiocyanates and is highly enriched in cruciferous vegetables. Our previous study showed that resveratrol, when used at high concentrations, inhibited cell proliferation, caused the cell cycle arrest and induced apoptotic cell death in glioma cells. In the current study, we tested the effect of combination treatment with resveratrol and sulforaphane, when both were used at low concentrations, on cell proliferation, migration and death in human U251 glioma cells. Our study shows that combination treatment with resveratrol and sulforaphane inhibits cell proliferation and migration, reduces cell viability, induces lactate dehydrogenase release, decreases pro-survival Akt phosphorylation and increases caspase-3 activation. The use of combination of bioactive food components, such as resveratrol and sulforaphane, may be a viable approach for the treatment of glioma.

Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Glioma; Humans; Isothiocyanates; Resveratrol; Stilbenes; Sulfoxides; Thiocyanates

We have previously reported that breast cancer resistance protein (BCRP) is involved in the transport of phase II metabolites of the food carcinogen benzo[a]pyrene (BP) in the human intestinal cell line Caco-2. Furthermore, the expression of BCRP seemed most likely to be aryl hydrocarbon receptor (AhR) dependent. Since numerous plant-derived anticarcinogens with AhR-agonistic activity have been identified to date, in the present study we investigated the effects of naturally occurring dietary compounds and tert-butyl hydroquinone (TBHQ) for their effects on BCRP expression. In Caco-2 cells, the most pronounced induction of BCRP expression could be observed after treatment with TBHQ (100 microM), dibenzoylmethane (DBM, 50 microM), and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) decreased BCRP expression. On mRNA level, quercetin, chrysin, flavone, and indole-3-carbinol showed a strong inducing effect, while genistein had no effect on BCRP mRNA expression. Curcumin and resveratrol showed a strong effect on BCRP induction in MCF-7 wild-type cells but no response in AhR-deficient MCF-7AHR(200) cells, supporting our hypothesis that BCRP is regulated via AhR-dependent signaling pathways. Inhibition of proteasome-mediated degradation of ligand-activated AhR caused a "superinduction" of BCRP mRNA. Antioxidant responsive element activators sulforaphane and diethylmaleate (DEM) had no inducing effect on BCRP mRNA expression. Caco-2 cells pretreated with quercetin or DBM showed an enhancement of apically transported benzo[a]pyrene-3-sulfate, indicating that induced BCRP was functionally active. In conclusion, apart from the modulation of detoxifying enzymes in the intestine, induction of BCRP by dietary constituents may contribute to the detoxification of food-derived procarcinogens such as BP.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Benzo(a)pyrene; Biological Transport; Caco-2 Cells; Catechin; Cell Line, Tumor; Chalcones; Flavonoids; Gene Expression; Humans; Hydroquinones; Indoles; Isothiocyanates; Maleates; Molecular Structure; Neoplasm Proteins; Plant Extracts; Quercetin; Receptors, Aryl Hydrocarbon; Resveratrol; RNA, Messenger; Silymarin; Stilbenes; Sulfoxides; Thiocyanates; Transfection

Potential chemopreventive effects of naturally occurring agents were investigated using a new 16-week medium-term pancreatic carcinogenesis models in hamsters. Male 6-week-old Syrian hamsters were subcutaneously injected with 10mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) four times within a week, and fed a diet supplemented with 80ppm benzyl isothiocyanate (BITC), 80ppm sulforaphane (SFN) or 10ppm resveratrol (RES) during the initiation or post-initiation stages. For the initiation stage, each chemical was given for 3 weeks including 1 week before and after the BOP injections. With post-initiation exposure, the groups were changed from basal diet 1 week after the last BOP injection, and then fed each chemical for 14 weeks. All the animals were sacrificed after 16 weeks. The multiplicities of combined pancreatic lesions including atypical hyperplasias and adenocarcinomas were significantly decreased by BITC and SFN given in the initiation but not the post-initiation stage. On the other hand, RES, a naturally occurring inhibitor of cyclooxygenase-2 (COX-2) reported chemopreventive effects, failed to show significant effects on pancreatic carcinogenesis in either the initiation or post-initiation stages. Our data suggest that the naturally occurring isothiocyanates BITC and SFN can block BOP-initiation of hamster pancreatic carcinogenesis.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Carcinogenicity Tests; Carcinogens; Cell Transformation, Neoplastic; Cricetinae; Cyclooxygenase 2; Diet; Injections, Subcutaneous; Isothiocyanates; Male; Membrane Proteins; Mesocricetus; Neoplasms, Experimental; Nitrosamines; Pancreatic Neoplasms; Resveratrol; Stilbenes; Sulfoxides; Thiocyanates