In Vitro Determination of Valproic Acid and Cisplatin Combination Antitumor Effect on Neuroblastoma Tumors Viability

Abstract

Neuroblastoma (SH-SY5Y) is one of the most common solid tumors in children, with aggressive and resistant features. Valproic acid (VPA) is a histone deacetylase inhibitor (HDAC) and is thought to have antitumoral activity. The aim of the current study is the evaluation of valproic acid and cisplatin (CSP) combination antitumor effects on SH-SY5Y. For this aim, the different doses of cisplatin (5, 10, and 15 μg/ml), VPA (5mM), and CSP (5, 10 and 15 μg/ml) + VPA (5 mM) were applied on SH-SY5Y tumor cell culture for 24 hours. For evaluation of cell viability, apoptosis, antioxidant and oxidant status, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), Anexin-V-FITC apoptosis, Total Antioxidant Capacity (TAC) and Total Oxidant Status (TOS) tests were done 24 hours after drug administration. According to our results, the combination of 15 μg/ml cisplatin and 5 mM VPA reduced cell viability and increased apoptosis status, compared with the negative control group (P<0.05). Our studies showed valproic acid increased the cisplatin effect and reduced the viability of tumor cells. The combination of VPA + CSP is more effective than only using cisplatin. In the light of these data, it is thought that the efficacy of VPA + CSP combined therapy should be investigated more comprehensively with in vivo studies.