Novel Poly (ADP-Ribose) Polymerase Inhibitor AZD2461 Combined with Valproic Acid Exerts Mild Antagonistic Effects in Hela Cells

Abstract

Background: Treatments of advanced cervical cancer are limited to pelvic radiation and chemotherapy while outcomes are disappointing. Poly (ADP-ribose) polymerase inhibitors are highly toxic to cells with defects in DNA repair pathways. The purpose of the current study was to evaluate whether the combination of AZD2461 as a novel poly (ADP-ribose) polymerase 1 inhibitor and a histone deacetylase inhibitor, valproic acid, could be efficacious in Hela cells harboring no mutations in DNA repair pathways. Methods: Cell morphology assay and MTT viability test were performed to determine cytotoxic effects of AZD2461 and valproic acid, separately and in combination. The combination effects were measured using the Chou-Talalay's method. Results: Although the analysis of cell morphology revealed that the combination of the two inhibitors could decrease the viable cells compared to each drug separately, MTT results showed that there was a mild antagonistic effect in the affected fractions of AZD2461/valproic acid-treated Hela cells at all effective doses (CI > 1.1). Conclusions: Our findings from this preliminary study conducted in Spring 2018 suggest that combining valproic acid with AZD2461 exerts mild antagonistic effects on Hela cells harboring no substantial defects in DNA repair pathways.