Demethylation and Re-Expression of Tumor Suppressor Genes: A Novel Approach for Cancer Therapy

In this study, we demonstrated that a combination therapy using suboptimal doses of HDACi and calpeptin, an inhibitor of calpain, produced synergistic type growth inhibition and reduced cancer cell motility in cancer cells. We hypothesize that the re-expression of tumor suppressor genes by demethylation and other mechanisms sensitize the cells and allows for apoptotic death. We are investigating ERK and Akt signaling pathway-mediated modulation of methylation-demthylation and regulation of DNMTs.