Combinatorial effects of PARP inhibitor PJ34 and histone deacetylase inhibitor vorinostat on leukemia cell lines.

BACKGROUND Poly (ADP-ribose) polymerase (PARP) inhibitors and histone deacetylase (HDAC) inhibitors are new promising anticancer drugs. The aim of the present study was to investigate the effect of combination treatment with PARP inhibitor PJ34 and HDAC inhibitor vorinostat on human leukemia cell lines. MATERIALS AND METHODS Proliferation, apoptosis, mitochondrial membrane potential (ψm) and cell cycle were assessed in HL60, MOLT4, U937 and K562 cells cultured with each drug alone and with both drugs. RESULTS PJ34 alone at 0.2-0.4 μM did not influence the examined parameters. Vorinostat alone at 1.0-2.5 μM reduced proliferation, increased apoptosis rate, lowered ψm and increased the percentage of sub-G1 cells in all cell lines. Incubation with both drugs caused further inhibition of proliferation and increase in apoptosis associated with a decrease in ψm and sub-G1 arrest in HL60, MOLT4 and K562 cells, but not in U937 cells. CONCLUSION Combination of PARP and HDAC inhibitors can exert a synergistic effect on inhibition of proliferation and increase apoptosis of leukemia cells.