<i>Trans</i>-Resveratrol Alters Mammary Promoter Hypermethylation in Women at Increased Risk for Breast Cancer

Zhu, Weizhu; Qin, Wenyi; Zhang, Ke; Rottinghaus, George E.; Chen, Yin Chieh; Kliethermes, Beth; Sauter, Edward R.

doi:10.1080/01635581.2012.654926

Cited by 203 publications

(134 citation statements)

References 35 publications

(41 reference statements)

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“…Four studies investigated supposed beneficial effects of resveratrol on markers of oxidative stress in obese subjects (4 weeks, 150 mg resveratrol) (De Groote et al, 2012), on methylation of cancerrelated genes in mammary ductoscopy specimen of 39 adult women with an increased breast cancer risk (12 weeks, 100 mg resveratrol) (Zhu et al, 2012), on endothelial function in adults with metabolic syndrome (3 months, 100 mg resveratrol) (Fujitaka et al, 2011), or on glucose homeostasis, inflammatory markers, resting energy rate, oxidation rate of lipids (4 weeks 1.5 g resveratrol/day) (Poulsen et al, 2013), without or with very limited parameters relevant for the safety assessment such as blood lipids, blood pressure or ALT which were not altered by the treatment. The Panel notes that these four studies provide no evidence for the safety of the NF.…”

Section: Human Studiesmentioning

confidence: 99%

Safety of synthetic trans‐resveratrol as a novel food pursuant to Regulation (EC) No 258/97

Products¹

2016

EFS2

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Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked for an opinion on the safety of synthetic trans-resveratrol as a novel food with a purity of ≥99% (w/w). The Panel considers that the information provided on the composition and specifications of the novel food is sufficient. The applicant intends to market the novel food as a food supplement in capsule or tablet form at daily doses up to 150 mg/day. The Panel considers that resveratrol does not have a nutritionally relevant role in the human diet and that the consumption of the novel food is not nutritionally disadvantageous. In accordance with the EFSA Scientific opinion on genotoxicity testing strategies, the Panel considers that the negative in vivo genotoxicity assay is sufficient to rule out the concern based on the positive in vitro chromosomal aberration tests.Reduced body weight gain is seen consistently in animal studies. On the basis of the BMDL 05 of 344 mg/kg body weight (bw) per day derived from body weight data of female rats in a subchronic toxicity study and the intended intake of 150 mg/day, the margin of exposure is 172. For pregnant rats, it is below 62. Considering the weight of evidence, the Panel concludes that the intended intake level of 150 mg/day for adults does not raise safety concerns. The Panel notes that diarrhoea or other gastrointestinal symptoms were reported in four uncontrolled intervention studies at doses of 1 g resveratrol/day or higher. The Panel considers that the metabolite trans-resveratrol sulfate could inhibit CYP enzymes in humans and may interact with medicines which are mainly metabolised by CYP2C9. The Panel concludes that the novel food, synthetic trans-resveratrol, is safe under the proposed conditions of use.

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Section: Human Studiesmentioning

confidence: 99%

Safety of synthetic trans‐resveratrol as a novel food pursuant to Regulation (EC) No 258/97

Products¹

2016

EFS2

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“…This has important implications for the treatment of women with breast cancer resistant to hormonal therapy. It has also been described as a DNA demethylating agent in breast tumors and breast carcinoma cell lines (Zhu et al 2012). It has recently been described that resveratrol synergizes with curcumin to inhibit colon cancer growth in mouse models, suggesting a better response to chemopreventive agents (Majumdar et al 2009).…”

Section: Resveratrolmentioning

confidence: 97%

Therapeutic Action of Phytochemicals on Cancer Stem Cells

Leis¹,

Gumuzio²,

Martín³

2013

Mitochondria as Targets for Phytochemicals in Cancer Prevention and Therapy

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The cancer stem cell (CSC) concept has important implications not only for our understanding of carcinogenesis, but also for the development of cancer therapeutics. There is a growing body of preclinical evidence that cancer stem cells contribute to chemotherapy and radiation resistance in breast cancer. The use of drugs that interfere with stem cell self-renewal represents the strategy of choice, but also a great challenge because cancer stem cells and their normal counterparts share many pathways. Dietary compounds have been used in cancer prevention for decades, and some of these compounds target specific mechanisms that control CSC self-renewal. However, to date, no significant impact of CSCs on clinical outcome has been identified. The new paradigm imposed by the CSC model may change the way therapeutic effects are measured in clinical trials, stressing the effect on overall survival over just rapid tumor size reduction. In this chapter, we present the concept of cancer stem cell, mechanisms of conventional anticancer treatment resistance, and how dietary compounds may be used to target the self-renewal capability of CSCs.

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“…In breast carcinomas, resveratrol inhibited cancer proliferation by demethylation of tumor suppressor RASSF-1α gene promoter (Zhu et al 2012). Aromatic hydrocarbon receptor (AhR) binds environmental xenobiotics and food compounds, and resveratrol acts as a potent dietary AhR antagonist.…”

Section: Stilbenoidsmentioning

confidence: 99%

Epigenetic Impact of Bioactive Dietary Compounds in Cancer Chemoprevention

Šupić

Wagner

Magić

2016

Critical Dietary Factors in Cancer Chemoprevention

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Epigenetic changes refer to modifications caused by heritable but potentially reversible changes in gene expression not coded in the DNA sequence. Evidence has been provided that various environmental factors and dietary bioactive compounds contribute to cancer development through epigenetic mechanisms. The main mechanisms of epigenetic control in mammals are DNA methylation, histone modifications, and RNA silencing through noncoding RNAs. The inhibition of DNA methyltransferases (DNMTs) involved in DNA methylation of CpG-rich regions of gene promoters and various enzymes involved in the chromatin condensation such as histone deacetylases (HDACs) have been recognized as potent strategies for cancer therapy and chemoprevention. Treatments using natural compounds such as green tea polyphenols, soy isoflavones, curcumin, resveratrol, isothiocyanates, and butyrate (an intestinal product from dietary fiber) modulate DNMT or HDAC gene expression and/or protein levels and activities, indicating that natural compounds could have strong potential to reverse epigenetic changes, without the adverse toxic effects associated with synthetic epigenetic inhibitors used in chemotherapy. Further characterization of the chemopreventive properties of various dietary bioactive compounds is warranted to potentially establish the clinical utility of dietary factors as anticancer compounds either alone or in combination with other dietary factors or clinically relevant therapeutics. Moreover, these characterizations are useful for personalized dietary recommendations and chemopreventive strategies for reducing cancer incidence.

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Trans-Resveratrol Alters Mammary Promoter Hypermethylation in Women at Increased Risk for Breast Cancer

Cited by 203 publications

References 35 publications

Safety of synthetic trans‐resveratrol as a novel food pursuant to Regulation (EC) No 258/97

Safety of synthetic trans‐resveratrol as a novel food pursuant to Regulation (EC) No 258/97

Therapeutic Action of Phytochemicals on Cancer Stem Cells

Epigenetic Impact of Bioactive Dietary Compounds in Cancer Chemoprevention

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