Resveratrol Protects Breast Health

TUCSON, Ariz.The aromatic hydrocarbon receptor (AhR) contributes to the etiology of various types of cancers. In a recent study at the University of Arizona, researchers investigated estrogen receptor-alpha (ER alpha)-positive and BRCA-1 wild-type MCF-7 breast cancer cells influence of AhR activation with the agonist 2,3,7,8 tetrachlorobenzo(p)dioxin (TCDD) on epigenetic regulation of the BRCA-1 gene, a tumor suppressor involved in repair of DNA damage, and the preventative effects of resveratrol (J Nutr. 2010;140(9):1607-14). Activation and recruitment of the AhR to the BRCA-1 promoter hampers 17 beta -estradiol (E2)dependent stimulation of BRCA-1 transcription and protein levels. These inhibitory effects are paralleled by reduced occupancy of ER alpha, acetylated histone (AcH)-4 and AcH3K9. Conversely, the treatment with TCDD increased the association of mono-methylated-H3K9, DNA-methyltransferase-1 (DNMT1) and methyl-binding domain protein-2 with the BRCA-1 promoter and stimulated the accumulation of DNA strand breaks. The AhR-dependent repression of BRCA-1 expression was reversed by small interference for the AhR and DNMT1 or pretreatment with Res, which reduced TCDD-induced DNA strand breaks. Researchers concluded epigenetic silencing of the BRCA-1 gene by the AhR is preventable with resveratrol and provide the molecular basis for the development of dietary strategies based on natural AhR antagonists.