l-Arginine Reduces Cell Proliferation and Ornithine Decarboxylase Activity in Patients with Colorectal Adenoma and Adenocarcinoma

Abstract

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.Colorectal carcinoma (CRC) is one of the most common cancers in the world, and colorectal adenoma (CRA) is known to be a precursor of both sporadic and hereditary CRC. Recent studies have shown that the frequency of adenomas in a population with an increased risk of CRC is higher as compared with that in the general population; moreover, patients with the so-called hereditary nonpolyposis syndrome also had an earlier onset of adenomas and faster progression to cancer (1). It is widely accepted that environmental factors, particularly dietary factors, are involved in the etiology of CRC. A high intake of fat, red meat, and energy have not only been associated with an increased risk of CRC (2 -5), but have also influenced the 5-year survival in the patients who underwent surgical treatment for CRC (6). Therefore, developing strategies to decrease the incidence of CRC and improve its prognosis by changing the diet or certain dietary components have currently become a hot topic of study. The focus on L-arginine supplements has been increasing in recent years.L-Arginine, a semiessential amino acid, is required for the synthesis...

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