Abstract

Colorectal cancer (CRC) is one of the frequently diagnosed cancers worldwide. Currently used chemotherapeutic drugs have several side effects. Histone deacetylase (HDAC) enzyme inhibitors possess potential anti-cancer effects. Therefore, we investigated the cytotoxic potential of sodium valproate, a HDAC inhibitor in human colorectal adenocarcinoma (HT-29) cells. MTT assay was used to analyze the cytotoxicity of HT-29 cells. Intracellular reactive oxygen species (ROS) induction was evaluated by dichloro-dihydro-fluorescein diacetate staining. Dual staining with acridine orange/ethidium bromide was used to investigate the morphology-related apoptotic cell death. Mitochondrial membrane potential was analyzed by rhodamine 123 staining. E-cadherin protein expression was examined by immunofluorescence staining. Sodium valproate at 2 and 4mM/mL treatments significantly induced cytotoxicity. Increased intracellular ROS expression was observed in the cells treated with sodium valproate. This treatment also induced mitochondrial dissipation, apoptosis-related morphological damage, and E-cadherin expression in HT-29 cells. Our present results suggest that sodium valproate is cytotoxic to HT-29 cells due to its pro-oxidative and apoptosis inducing potential. Sodium valproate can be used as an adjuvant along with standard chemotherapeutic agents in CRC patients after necessary in vivo and clinical studies.

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