Effect of arginine on angiogenesis induced by human colon cancer: in vitro and in vivo studies.
This study investigated the effect of arginine (Arg) supplementation on angiogenesis in human colon cancer. The in vitro study investigated the effects of different Arg levels and inducible nitric oxide (iNO) synthase inhibitor on angiogenic protein expressions stimulated by SW480 cells. The results showed that the production of vascular endothelial growth factor (VEGF), basic fibroblast growth factor with 100 and 1000 micromol/L Arg and matrix metalloproteinase (MMP)-2 with 1000 micromol/L Arg was lower than that with 0 and 50 micromol/L Arg. Inhibition of iNO resulted in higher angiogenic protein expressions comparable with groups with low Arg administration, indicating that Arg administration at levels similar to or higher than physiological concentrations reduced the progression of colon cancer, and iNO may partly play a role in reducing angiogenesis. The in vivo study used a human colon cancer xenograft model in nude mice. Mice were inoculated with 1x10(7) SW480 cells and assigned to two groups. The control group was fed a semipurified diet, while the experimental group was supplied an Arg-supplemented diet. After 5 weeks, tumors were harvested and spleens were excised for further analysis. Results showed that the MMP-2, MMP-9 and VEGF receptor levels in tumors were significantly lower, whereas tumor NO levels and spleen natural killer (NK) cell activities were higher in the Arg group than in the control group. These results were consistent with the in vitro study that dietary Arg supplementation inhibits the progression of colon cancer possibly by increasing NO secretion and consequently enhancing NK cell activity.
Yeh
Chiu-Li
CL
Institute of Nutrition and Health Sciences, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
Pai
Man-Hui
MH
Li
Cheng-Chung
CC
Tsai
Yu-Ling
YL
Yeh
Sung-Ling
SL
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D039564:Integrin alphaV / Q000096:biosynthesis; D039661:Integrin beta3 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D039564:Integrin alphaV; D039661:Integrin beta3; D042461:Vascular Endothelial Growth Factor A; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9