Inhibition of gastric cancer cell growth by arginine: molecular mechanisms of action.
OBJECTIVE
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.
Nanthakumaran
Shayanthan
S
School of Medicine and Dentistry, College of Life Sciences and Medicine, University of Aberdeen, Medical School, Foresterhill, Aberdeen, UK.
Brown
Iain
I
Heys
Steven D
SD
Schofield
Andrew C
AC
D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D015153:Blotting, Western; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013997:Time Factors
D001120:Arginine; C505530:CASP8 protein, human; D053181:Caspase 8