Vitamin C induces apoptosis in AGS cells by down-regulation of 14-3-3 sigma via a mitochondrial dependent pathway

Abstract

Ascorbic acid (vitamin C) is an essential component of most living cells. Apart from antioxidant activity, it has been reported to inhibit cancer cell growth in vitro in human cancer cells. However, the cellular mechanism underlying anticancer activity has not been fully elucidated. In this study, vitamin C showed a cytotoxic effect on human gastric cancer cell line ACS (LD50 300 mu g/ml). Further, flow cytometry analysis showed that vitamin C increased the sub-G1 (apoptosis) population and apoptosis confirmed by fluorescein isothiocyanate-Annexin V double staining in ACS cells. Moreover, specific immuno-blotting revealed the expression of the phosphorylated form of Bad (S136), 14-3-3 sigma, pro-caspases-3, -6, -8, and-9 protein levels were significantly decreased and Bax/BcI-xL ratio was increased in a dose-dependent manner. Also, wound healing assay results showed that vitamin C inhibited AGS cell proliferation. These findings suggest that vitamin C induces apoptosis and might be a potential therapeutic agent for gastric cancer. (C) 2012 Elsevier Ltd. All rights reserved.