α-Lipoic Acid Induces Intrinsic Apoptosis in Human Oral Squamous Carcinoma Cells
Abstract Oral squamous cell carcinoma is one of the leading cancers in India and it is responsible for significant morbidity and mortality. α -lipoic acid, a co-factor for several metabolic enzymes, suppresses the tumor growth. In this study, we investigated the α-lipoic acid-induced cytotoxicity and apoptosis in human oral squamous carcinoma (SCC-25) cells. α-lipoic acid treatments were given to SCC-25 cells for 24 h and cell proliferation was evaluated by MTT assay. The reactive oxygen species expression was examined by dichloro-dihydro-fluorescein diacetate assay. Apoptosis-related morphological changes were detected by dual staining. Cytochrome c and RAS (H-Ras) expression was measured by dual staining and RT-PCR respectively. Intrinsic apoptosis-related markers are analyzed using qPCR.α-lipoic acid inhibited SCC-25 cell proliferation in a concentration-dependent manner. This treatment also increased intracellular reactive oxygen species expression and the percentage of apoptotic cells (up to 70% of the cell population). Dual staining further confirms cytochrome c cytosolic expression. The oncogene H-Ras protein and gene expression was also down-regulated upon α-lipoic acid treatment in SCC-25 cells. qPCR analysis further confirms α-lipoic acid-induced an upregulation of bax, Apaf-1, caspase 3 and − 9, pro-apoptotic gene expressions and downregulation of bcl-2, an anti-apoptotic gene expression. The present results suggest that α-lipoic acid has cytotoxic and pro-apoptotic potential and it also downregulates H-Ras oncogene expression in human oral squamous carcinoma cells. α-lipoic acid may have promising role in the treatment of human oral squamous carcinoma.