Abstract
Interest in cancer epigenetics has arisen from the fact that epigenetic processes affect many aspects of tumor formation and progression. The reversibility of epigenetic changes that may arise in early tumorigenesis is an important aspect of their potential in approaches for cancer prevention. Many of the components of the human diet have bioactive effects that lead to reversal of epigenetic aberrations in cancer. We have found that both (-)-epigallocatechin-3-gallate (EGCG) from green tea and sulforaphane (SFN) from cruciferous vegetables are able to down-regulate telomerase in breast cancer cells. This occurs through epigenetic modifications of the promoter region of hTERT, the gene that encodes the catalytic subunit of telomerase. Since telomerase promotes tumor formation and is active in about 90% of cancers, this epigenetic inhibition of its catalytic subunit gene may have considerable potential in breast cancer prevention. Our studies also indicate that these bioactive dietary compounds are able to convert estrogen-receptor (ER)-negative breast cancer cells to ER-positive breast cancer cells and to prevent the formation of highly lethal ER-negative breast cancer. This occurs through epigenetic modifications of the ERalpha gene in response to EGCG and SFN. These findings have significance in that ER-positive cells are amenable to breast cancer prevention or therapy with compounds such as tamoxifen while ER-negative cells confer few preventive or treatment options for patients. Moreover, our studies have also indicated that EGCG and SFN have additive or synergistic epigenetic effects on cancer prevention and that the oral administration of green tea polyphenols and SFN-rich broccoli sprouts inhibits the formation of breast cancer in mice. These results are important because the combination of these dietary products may have potential in lowering their efficacious consumption and increase their utility for breast cancer prevention in humans.
Citation Format: Trygve Tollefsbol, Yuanyuan Li. Epigenetic targets of sulforaphane and epigallocatechin gallate in cancer prevention. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN12-03.