Abstract
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.
- Received January 13, 2014.
- Revision received February 11, 2014.
- Accepted February 12, 2014.
- Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved