Title of article :
Mild antagonistic effect of Valproic acid in combination with AZD2461 in MCF-7 breast cancer cells
Author/Authors :
Sargazi ,Saman Cellular and Molecular Research Center - Zahedan University of Medical Sciences - Zahedan, Iran , Saravani , Ramin Cellular and Molecular Research Center - Zahedan University of Medical Sciences - Zahedan, Iran , Mirinejad , Shekoufeh Cellular and Molecular Research Center - Zahedan University of Medical Sciences - Zahedan, Iran , Kooshkaki , Omid Department of Immunology - School of Medicine - Birjand University of Medical Sciences - Birjand, Iran , Zavar Reza , Javad Department of Clinical Biochemistry - School of Medicine - Shahid Sadoughi University of Medical Sciences - Yazd, Iran , Zarei jaliani , Hossein Department of Medical Genetics - School of Medicine - Shahid Sadoughi University of Medical Sciences - Yazd, Iran , Meshkini , Fatemeh Student Research committee - Shahid Sadoughi University of Medical Sciences - Yazd, Iran
Pages :
6
From page :
1
To page :
6
Abstract :
Breast cancer (BC) is a complex disease, but current treatments are not efficient enough considering increased relapse and decreased survival rate among patients. Poly (ADP-ribose) polymerase inhibitors are recently developed anticancer agents which target cells with defects in homologous recombination (HR) pathway. This study wishes to assess whether the combination of AZD2461 as a newly developed PARP1 inhibitor and valproic acid (VPA), a histone deacetylase inhibitor could effectively reduce the growth of MCF-7 cells with no fundamental DNA repair defect. Methods: Both trypan blue dye exclusion assay and MTT viability test were used to evaluate cell death. γ-H2AX levels, as a marker of DNA repair, were measured using in cell ELISA method. The Studentchr('39')s t-test and non-parametric analysis of variance (ANOVA) were applied for our data analyses where p-value <0.05 was considered statistically significant. Results: As calculated by CompuSyn software, IC50 values for VPA and AZD2461 were 4.89 mM and 42.83 µM respectively following 48 hours treatment. Also, the trypan blue exclusion assay results showed a concentration- and time-dependent decrease when MCF-7 cells were treated with both agents (p<0.05). Combination analysis showed a mild antagonism (CI>1.1) while γ-H2AX levels found not to be significantly increased in MCF-7 cells co-treated with VPA+AZD2461 compared to each agent alone (p=0.29). Conclusion: Our findings revealed that the combination of VPA and AZD2461 could decrease cell viability of MCF-7 cells, but it was not able to significantly increase unrepaired DNA damage sites. The mechanism responsible for drugs combination was not of synergism or addition. Determining the type of involved cell death mechanisms might be followed in further studies.
Keywords :
AZD2461 , Combination therapy , Valproic acid , Breast cancer
Journal title :
Medical Journal of the Islamic Republic of Iran
Serial Year :
2019
Record number :
2501365
Link To Document :
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