The potential therapeutic effect of NG-hydroxy-nor-L-arginine in 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

• Published in: Experimental and molecular pathology 2019-12, Vol.111, p.104316, Article 104316
• Main Authors: Avtandilyan, Nikolay, Javrushyan, Hayarpi, Mamikonyan, Anahit, Grigoryan, Anna, Trchounian, Armen
• Format: Article
• Language: English
• Subjects: 7,12-dimethylbenz(a)anthracene induced, anti-tumor potential; Arginase; Breast cancer; NO-synthase; Nor-NOHA
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2019.104316

Advances in our understanding of the metabolism and molecular functions of arginine and their alterations in cancer have led to resurgence in the interest of targeting arginine catabolism as an anticancer strategy. Therefore, arginase inhibitors have been proposed as a way to treat cancer. In this study, the anti-tumor potential of the arginase inhibition by NG-hydroxy-nor-L-arginine (nor-NOHA) (3 mg/kg/day, i.p.), administered for 5 weeks (parallel tumors development, every 3th day) against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in rats has been investigated. Treatment by nor-NOHA has obvious inhibition effects on development of carcinogenesis in rats was shown. That was seen in downregulation of rats' tumors size and number, mortality rate, in stopped alteration of tissue histopathology, in decrease of polyamines, NO and MDA (malondialdeide) concentrations (in blood). Results have shown arginase and NO-synthase can cooperate to restrain quantities of polyamines and NO for cancer progression. The results obtained can serve as a base to use this model for determination of productive, noncytotoxic antitumor and immune modulating concentration of anticancer agents. Perspectives of targeting arginase and NOS in cancer management can ground application in clinical medicine. •Polyamines and NO quantity downstream by nor-NOHA attenuate tumor growth, quantity and mortality rate.•Histopathological alteration of breast tissues is stopped by nor-NOHA treatment.•Arginase activity inhibition by nor-NOHA in vivo does not cause oxidative stress and hyperammonemia.•Arginase and NOS cooperate to restrain polyamine and NO for cancer progression.