Inhibition of gastric cancer cell growth by arginine: Molecular mechanisms of action

Background & aims: Immunonutrition, containing arginine as a key component, has been shown to enhance the immune system and significantly reduce infectious Complications in patients undergoing upper gastrointestinal surgery. Arginine, however, may also influence tumour cell behaviour. The aim of this study was to investigate the effects of arginine on tumour cell growth, invasion and modulation of expression of genes involved in these aspects of cell behaviour. Methods: A human gastric cancer cell line (AGS) was grown in vitro and Supplemented with arginine (2, 4, 8,16 and 32 mM) for 24,48 and 72 h. The effect of arginine on cell growth (MTT assay), apoptosis (DAPI staining), invasion (Matrigel assay), gene expression (cDNA microarray analysis and RT-PCR) and protein expression (western analysis) was determined. Results: These studies demonstrated that arginine caused a decrease in AGS cell growth via induction of apoptosis. Whilst arginine decreased cell growth, no significant effect on the invasive potential of AGS cells was noted. Subsequent gene expression analysis demonstrated that arginine increased the expression of caspase 8, which was validated at the protein level. Conclusions: These results suggest that that inhibition of AGS cell growth by arginine is mediated through caspase 8 activation of apoptosis. (c) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.