Epigenetic agents as an adjunct to active chemotherapy in hematological tumor cell lines

Abstract

Epigenetic therapy is a new promising area in cancer research that is based on the use of a series of molecules capable of affecting tumor cell growth, differentiation and death by modifying the cellular mechanisms underlying the control of gene expression. Significant enhancement of traditional anticancer drug effects has been also reported by several authors. Our recent research focused on the identification of new epigenetic agent-containing drug combinations to be employed in the therapy of leukemia. The results showed that the new combination of an histone deacetylase (HDAC) inhibitor and the ribonucleotide reductase (RR) inhibitor 3’-methyl-adenosine (3’-Me-Ado) is endowed with a significant antitumor activity against promyelocytic leukemia cells. This effect was dependent not only by the HDAC inhibitors-mediated enhancement of drug-induced apoptosis, but also by the ability of these pleiotropic agents to inhibit the activity of the RR enzyme. Studies are ongoing to verify the feasibility of creating new bifunctional agents containing both an RR and an HDAC inhibitor within the same molecule, so that they can reproduce the effects of this combination and furnish an easier and effective therapeutic modality in view of a possible future use in the clinics.