L-arginine reduces cell proliferation and ornithine decarboxylase activity in patients with colorectal adenoma and adenocarcinoma

Clin Cancer Res. 2007 Dec 15;13(24):7407-12. doi: 10.1158/1078-0432.CCR-07-0751.


Purpose: Evidence suggests that the majority of colorectal carcinomas arise from adenomas, and L-arginine suppresses colorectal tumorigenesis. We suppose that L-arginine may inhibit the process of carcinogenesis from colorectal adenoma to adenocarcinoma. The aim of this study was to investigate the effects of L-arginine on the formation and development of colorectal tumors.

Experimental design: We selected 60 patients with colorectal cancer and 60 patients with colorectal adenoma (CRA) and divided them into four groups of 30 patients each. We gave 30 g (120 mL) of L-arginine everyday for 3 days to the test groups, whereas L-arginine was substituted by 5% glucose in the control groups. The expression of the proliferating cell nuclear antigen, survivin, and nitric oxide synthase was examined immunohistochemically, and ornithine decarboxylase (ODC) activity was examined spectrophotometrically. Serum nitric oxide (NO) was detected by the Griess assay.

Results: In patients with CRA, the proliferating cell nuclear antigen and survivin labeling indexes and ODC activity of the tumor and paratumor mucosa in the L-arginine-treated group after L-arginine treatment were significantly lower as compared with the corresponding pretreatment values (P < 0.01). Moreover, inducible nitric oxide synthase expression in the tumor markedly increased after L-arginine treatment (P < 0.05). Serum NO levels in the patients with colorectal cancer were markedly higher than those in the patients with CRA, and L-arginine treatment was responsible for this increase (P < 0.05).

Conclusions: Our results show that L-arginine can restrain crypt cell hyperproliferation and the expression of survivin, an inhibitor of apoptosis protein. This suggests that L-arginine can block the formation and development of colorectal tumors, and this effect might be related to the increased serum NO concentration and decreased ODC activity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Adenoma / drug therapy*
  • Adenoma / enzymology
  • Adenoma / pathology
  • Arginine / therapeutic use*
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / pathology
  • Double-Blind Method
  • Female
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins
  • Male
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / drug effects
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / drug effects
  • Nitric Oxide / blood
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / drug effects
  • Ornithine Decarboxylase / drug effects*
  • Proliferating Cell Nuclear Antigen / drug effects
  • Survivin


  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proliferating Cell Nuclear Antigen
  • Survivin
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Ornithine Decarboxylase