Our recent work with different cancer cell types revealed that demethylation of CpG units in the upstream regions of tumor suppressor genes and genes inducing differentiation could be a tool to enhance susceptibility of these ceils to other cytotoxic drugs.The methylation patterns of similar genes in different types of cancers are different and the amount of demethylation produced by similar inhibitors varies in different cancer types.HDAC inhibitors (HDACi)are in clinical trial as anticancer agents and the use of these inhibitors in combination with other cytotoxic drugs are showing promising results.We recently observed that HDACi demethylate tumor suppressor genes such as p21 and p1 6 and genes involved in differentiation such as RAR beta2.Demethylation caused increased expression of these genes, resulting in cell cycle inhibition and induction of apoptosis.In an attempt to investigate the combinational effects of other cytotoxic drugs we determined that a natural non-toxic anti-carcinogenic isoflavonoid found in soybeans in combination with HDACi produced synergistic inhibition in MCF-7 breast cancer cells.We are currently investigating the signaling and epigenetic mechanism of this enhanced breast cancer cell growth inhibition in comparison to other cancer types.