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

PARP抑制剂PJ34与组蛋白去乙酰化酶抑制剂伏立诺他联合应用对白血病细胞株的作用

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作者:Ewa Jasek, Mariusz Gajda, Grzegorz J Lis, Małgorzata Jasińska, Jan A Litwin

Background

Poly (ADP-ribose) polymerase (PARP) inhibitors and histone deacetylase (HDAC) inhibitors are new promising anticancer drugs. The

Conclusion

Combination of PARP and HDAC inhibitors can exert a synergistic effect on inhibition of proliferation and increase apoptosis of leukemia cells.

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.

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