HISTONE DEACETYLASE (HDAC) INHIBITION MODULATES INTRACELLULAR DEOXYNUCLEOTIDES (DNTP) POOLS AND POTENTIATES THE ANTITUMOR EFFECTS OF THE RIBONUCLEOTIDE REDUCTASE (RR) INHIBITOR 3’- METHYL-ADENOSINE (3’-ME-ADO) IN PROMYELOCITIC LEUKAEMIA CELL LINES.

HDAC inhibitors are a new class of antitumor agents that were reported to enhance the cytotoxic effects of a number of classical anticancer drugs through multiple mechanisms. In particular, they are capable of modulating the expression of a series of key cellular genes leading to significant antiproliferative and apoptotic effects. However, which of the possible drug combinations would be the most effective and clinically useful is still to be determined. We treated the HL60 and NB4 promyelocitic leukaemia cells with a combination of the RR inhibitor 3’-Me-Ado and several hydroxamic acid–derived HDAC inhibitors, including the two recently synthesized molecules, MC1864 and MC1879, and the re…