Author/Authors :
Sargazi, Saman International Campus - Shahid Sadoughi University of Medical Sciences, Yazd, Iran , Saravani, Ramin Department of Clinical Biochemistry - School of Medicine - Zahedan University of Medical Sciences, Zahedan, Iran , Zavar Reza, Javad Department of Clinical Biochemistry - School of Medicine - Shahid Sadoughi University of Medical Sciences, Yazd, Iran , Zarei Jaliani, Hossein Protein Engineering Laboratory - Department of Medical Genetics - School of Medicine - Shahid Sadoughi University of Medical Sciences, Yazd, Iran , Mirinejad, Shekoufeh Cellular and Molecular Research Center - Zahedan University of Medical Sciences, Zahedan, Iran , Moudi, Mahdiyeh Genetics of Non-Communicable Disease Research Center - Zahedan University of Medical Sciences, Zahedan, Iran , Galavi, Hamidreza Department of Clinical Biochemistry - School of Medicine - Zahedan University of Medical Sciences, Zahedan, Iran
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 andMTT 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.
Keywords :
Cell Death , AZD2461 , Valproic Acid , Uterine Cervical Neoplasms
