Long-term genistein treatment of MCF-7 cells decreases acetylated histone 3 expression and alters growth responses to mitogens and histone deacetylase inhibitors

Long-term genistein treatment (LTGT) of MCF-7 cells markedly reduced the basal expression of acetylated histone 3 (H3) and the effects of HDACi's on increasing the levels of acetylated H3 protein. However, this was not correlated with a reduced expression of total H3 except after a high dose of VPA. LTGT inhibited growth of MCF-7 cells and the mitogenic responses to E2 and EGF. The growth inhibitory responses to HDACI's in the presence of E2 and EGF was significantly reduced in LTGT cells compared to control MCF-7 cells and there was evidence that LTGT maintained the protein levels of pro-caspase 9 in the presence of HDACi's. This study provides further evidence that oestrogenic substances can induce significant epigenetic changes to alter the dynamics of growth in breast cancer cell lines.