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

• Published in: Molecular and cellular biochemistry 2023-02, Vol.478 (2), p.261-275
• Main Authors: Avtandilyan, Nikolay, Javrushyan, Hayarpi, Ginovyan, Mikayel, Karapetyan, Anna, Trchounian, Armen
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Angiogenesis; Animals; Anions; Anthracene; Anticancer properties; Antitumor agents; Arginase; Biochemistry; Biomedical and Life Sciences; Body weight; Brain - metabolism; Breast cancer; Cancer; Cardiology; Care and treatment; Cell death; Enzyme Inhibitors - pharmacology; Health aspects; In vivo methods and tests; Life Sciences; Medical Biochemistry; Neoplasms - drug therapy; NG-Nitroarginine methyl ester; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitric-oxide synthase; Oncology; Polyamines; Prevention; Rats; Spinal cord; Tumors
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-022-04489-y

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, NH 4 + 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.