Vitamin C induces apoptosis in AGS cells by down-regulation of 14-3-3σ 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 AGS (LD50 300μg/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 AGS cells. Moreover, specific immuno-blotting revealed the expression of the phosphorylated form of Bad (S136), 14-3-3σ, pro-caspases-3, -6, -8, and-9 protein levels were significantly decreased and Bax/Bcl-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.

• Authors: Arulkumar Nagappan, Kwang Il Park, Hyeon Soo Park, Jin A Kim, Gyeong Eun Hong, Sang Rim Kang, Do Hoon Lee, Eun Hee Kim, Won Sup Lee, Chung Kil Won, Gon Sup Kim
• Journal: Food chemistry (Food Chem) Vol. 135 Issue 3 Pg. 1920-8 (Dec 01 2012) ISSN: 1873-7072 [Electronic] England
• PMID: 22953941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• 14-3-3 Proteins
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Ascorbic Acid

Topics

• 14-3-3 Proteins (genetics, metabolism)
• Apoptosis (drug effects)
• Ascorbic Acid (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Humans
• Mitochondria (drug effects, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Signal Transduction (drug effects)
• bcl-2-Associated X Protein (genetics, metabolism)