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Sodium Valproate, a Histone Deacetylase Inhibitor, Provokes Reactive Oxygen Species–Mediated Cytotoxicity in Human Hepatocellular Carcinoma Cells

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Abstract

Background and Aim

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

Authors thank M/s. Anjan Drug Private Limited, Chennai, Tamil Nadu, India, for providing sodium valproate EP as gratis. Special thanks to Dr. S. Gheena, Department of Oral Pathology, Saveetha Dental College and Hospitals, Chennai, India, for the drug procurement procedures.

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Authors and Affiliations

  1. Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, 600 077, India

    Prabakaran Rithanya & Devaraj Ezhilarasan

  2. 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

    Devaraj Ezhilarasan

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PR and ED performed the research. PR reviewed the literature and drafted the manuscript, and ED corrected the manuscript, designed the figures, and submitted the manuscript.

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Correspondence to Devaraj Ezhilarasan.

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Rithanya, P., Ezhilarasan, D. Sodium Valproate, a Histone Deacetylase Inhibitor, Provokes Reactive Oxygen Species–Mediated Cytotoxicity in Human Hepatocellular Carcinoma Cells. J Gastrointest Canc 52, 138–144 (2021). https://doi.org/10.1007/s12029-020-00370-7

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