Studies on Wild Yam (Dioscorea villosa) Root Extract as a Potential Chemopreventive Agent for Breast Cancer

Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling are able to inactivate specific gene function which is considered as one of the mechanisms involved in breast cancer development [1]. Attempts have been made to develop demethylating epigenetic drugs (epi-drugs) that are able to reactivate the silenced gene and prevent breast cancer. The current synthetic epi-drugs are non-specific and able to induce adverse side effects. In an attempt to search new and safe gene-specific demethylating agents (epi-drugs) from natural products, this study aimed to evaluate the effects of wild yam (Dioscorea villosa) root extract in an estrogen receptor positive (ER+) breast cancer cell line (MCF-7). Two genes, DNA methyl transferase 3B (DNMT3B) and GATA3 which are reported to be over expressed in breast cancer cells were used for evaluation. Additionally, by using Methyl Primer Express V1.0 software (Applied Bioscience) we were able to identify 3 CpG rich sites in the promoter region of GATA3 and 1 site in DNMT3B. MCF-7 cells at about 70% confluency were exposed to various concentrations of wild yam root extract (0–50 ((igrave))g/ml) for 72h. After cell count, total RNA was extracted and used for GATA3 and DNMT3B mRNA analysis by quantitative real-time PCR (qPCR). Moreover, the promoter methylation pattern of a specific region of GATA3 gene was also analyzed. It was observed that wild yam root extract significantly reduced the cell proliferation in a dose-dependent manner. The mRNA expression of DNMT3B was significantly enhanced in a dose-dependent manner as observed by qPCR while GATA3 mRNA expression was unaltered. From our preliminary data, it was evident that wild yam root extract has the potential to be used as a cancer chemopreventive substance, however, to establish its efficacy as an epi-drug more studies are needed. Acknowledgements: Thanks go to the United States Department of Agriculture, Agriculture Research Service, Specific Cooperative Agreement No. 58–6408–2-0009. References: [1] Khan SI, Aumsuwan P, et al. (2011) Chemical Research in Toxicology, dx.doi.org.10.1021/tx200378c