Evaluation of epigenetic properties of dioscin and diosgenin isolated from wild yam (Dioscorea villosa) root extract

Previously, we have observed that wild yam root extract (WYRE) is able to enhance DNA methyltransferase (DNMT) mRNA expression in human breast cancer cells, MCF-7 (GATA3-positive, non-invasive, epithelial) and MDA-MB-231 (GATA3-negative, invasive, mesenchymal) followed by demethylation and activation of gata binding protein-3 (GATA-3). We hypothesize that WYRE was able to demethylate GATA-3 promoter and activate GATA-3. The present study was aimed to evaluate the epigenetic effects of two bioactive constituents of WYRE (dioscin and diosgenin) in MCF-7 and MDA-MB-231 cells. The anti-cell proliferative activity of dioscin (DC) and diosgenin (DG) was determined by treating the cells either with DC or DG for 72h. The IC50 is 3.85 uM for MCF-7 and 2.07 UM for MDA-MB-231 by DC and 29.35 uM for MCF-7 and 20.15 uM for MDA-MB-231 by DG. qPCR analysis of DNMT1, 3A, 3B, GATA3, ZFPM2, CDH1, MMP9, and VIM indicate that in response to DC (5.76 uM) DNMT1 mRNA remained unaltered in both cell lines whereas DNMT3A increased in MDA-MB-231. DNMT3B mRNA showed significant increase in both cell lines. Upon DG treatment (24.17 uM), DNMT1 remained unaltered in MCF-7 but increased in MDA-MB-231, while DNMT3A and 3B remained unaltered in both cells. Although in these cells, GATA3 mRNA expression remained unaltered by both compounds, ZFPM2, an upstream GATA-3 gene, was significantly increased only by DC. E-cadherin, a downstream gene of GATA-3 and a cellular transition marker, is also increased in both cell lines by DS (5.76 uM) but decreased by DG (24.17 uM). Other cell transition markers such as MMP9 remained unaltered in both, while VIM showed cell-specific response with an increase in MCF-7 and a decrease in MDA-MB-231. These data indicate that DS is more epigenetically effective than DG in breast cancer cells.