Anti-cancer effect of in vivo inhibition of nitric oxide synthase in a rat model of breast cancer

Abstract

Increased expression of nitric oxide synthase (NOS) is associated with different cancers such as cervical, breast, lung, brain, and spinal cord. Inhibition of NOS activity has been suggested as potential tool to prevent breast cancer. The anti-tumor therapeutic effect of L-nitro arginine methyl ester (L-NAME), NOS inhibitor, using in vivo models is currently under investigation. We hypothesized that L-NAME will show an anti-tumor effect by delaying a progression of breast cancer via a modulation of cell death and proliferation, and angiogenesis. We used a novel model of anti-cancer treatment by the administration of L-NAME (30 mg/kg in a day, intraperitoneal) injected every third day for five weeks to rat model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast tumor. Concentrations of nitrite anions, polyamines, malondialdehyde, NH₄⁺ levels, and arginase activity in the blood were decreased in DMBA + L-NAME-treated rats compared with DMBA rats. The mortality rates, tumor number, weight, and volume, as well as the histopathological grade of breast cancer were also significantly reduced. In addition, L-NAME treatment showed a delay in tumor formation, and in body weight compared with rats administrated only with DMBA. In conclusion, our data show that L-NAME is a promising anti-cancer agent to treat breast cancer, which can lead to development of anti-tumor therapeutic tools in future.

Keywords: 7,12-dimethylbenz[a]anthracene; Arginase; L-NAME; Nitric oxide; Polyamine; Tumor prevention.