0000000001205761
AUTHOR
P Franchetti
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…
Antitumor effects of novel co-drugs linking histone deacetylase and ribonucleotide reductase inhibitors in hematological tumors
Combination therapy is the mainstay of anticancer therapy due to the significant synergistic effects achievable. Now that anticancer drug research turned toward a more molecular targeted approach, the design of dual-target drugs appears to be a new promising strategy with the potential to improve the therapeutic efficacy of the single drug and to reduce the probability of drug induced resistance and cross resistance. In our previous work, we found that 3’-C-methyl-adenosine (3’-Me-Ado), developed by us as a potent ribonucleotide reductase (RR) inhibitor with antitumor activity against both human leukemia and carcinoma cell lines, elicited significant growth inhibitory and apoptotic synergis…
Epigenetic agents as an adjunct to active chemotherapy in hematological tumor cell lines
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 sign…