Rithanya Prabakaran, Ezhilarasan Devaraj
Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, 600 077, India.
Biomedical Research Unit and Laboratory Animal Centre, Saveetha Dental College (SDC), Saveetha Institute of Medical and Technical Sciences, No.162, PH Road, Chennai, Tamil Nadu, 600 077, India.
J Gastrointest Cancer. 2021 Mar;52(1):138-144. doi: 10.1007/s12029-020-00370-7.
Sodium valproate (SV), a novel class of histone deacetylases (HDACs) inhibitors commonly used as an antiepileptic drug. HDAC inhibitors are known to possess anticancer potentials. In this study, we investigated the cytotoxic potential of SV in human hepatocellular carcinoma (HepG2 cells) cell line.
MTT assay was used to analyze cytotoxicity. Intracellular ROS and cytochrome c expression were analyzed by fluorescence microscopy. Morphology-related apoptosis was analyzed by dual staining with acridine orange/ethidium bromide. Caspase 3 protein expression was investigated by Western blotting analysis.
Sodium valproate treatments in HepG2 cells caused significant and dose-dependent cytotoxicity. Intracellular ROS was remarkably increased in the cells which are treated with SV and caused early and late apoptosis as evidenced by dual staining. SV-treated cells expressed cytochrome c and caspase 3 protein expression.
These results suggest the cytotoxic potentials of SV in HepG2 cells. This study may give an important clue for the inclusion of SV as an adjuvant along with standard anticancer agents after necessary in vivo and clinical studies.
丙戊酸钠（SV）是一类新型的组蛋白去乙酰化酶（HDACs）抑制剂，常用作抗癫痫药物。已知HDAC抑制剂具有抗癌潜力。在本研究中，我们调查了SV对人肝癌（HepG2细胞）细胞系的细胞毒性潜力。
采用MTT法分析细胞毒性。通过荧光显微镜分析细胞内活性氧（ROS）和细胞色素c的表达。用吖啶橙/溴化乙锭双重染色分析形态学相关的细胞凋亡。通过蛋白质印迹分析研究半胱天冬酶3蛋白的表达。
丙戊酸钠处理HepG2细胞会导致显著的剂量依赖性细胞毒性。用SV处理的细胞中细胞内ROS显著增加，并导致早期和晚期细胞凋亡，双重染色证明了这一点。经SV处理的细胞表达细胞色素c和半胱天冬酶3蛋白。
这些结果表明SV对HepG2细胞具有细胞毒性潜力。本研究可能为在必要的体内和临床研究后将SV作为辅助药物与标准抗癌药物联合使用提供重要线索。
