Role of Endothelial Nitric Oxide Synthase in Breast Cancer

Abstract

Breast cancer (BC) is the most common form of carcinoma and a primary cause of morbidity and mortality globally. Oxidative stress represents as an important factor in carcinogenesis and may play a role in initiation and progression of tumors. Oxidative stress-induced NO• damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. It is caused by an unfavorable balance between reactive oxygen species/reactive nitrogen species (ROS/RNS) and antioxidant defenses. ROS/RNS are generated during normal cellular metabolism, as a result of the influence of various environmental factors, as well as during pathological processes.Nitric oxide (NO•) is a ubiquitous, short-lived free radical produced from L-arginine by nitric oxide synthases (NOSs), and isoforms of NOS exist, depending on the site of origin: endothelial (eNOS), neuronal (nNOS), mitochondrial (mtNOS), and inducible (iNOS). eNOS is responsible for the endothelial synthesis of NO• and has shown to modulate cancer-related events such as inflammation, angiogenesis, apoptosis, cell cycle, invasion, and metastasis. Genetic studies also showed that eNOS gene polymorphisms are associated with the development of breast cancer. Therefore, selective targeting of eNOS may prove a potential strategy for prevention and treatment of breast cancer.

The Role Of Nitric Oxide In Cancer Development & it`s Therapy

“…Because of their participation in many processes that are related to cancer cell formation and proliferation. Free radicals are characteristic of cancer (2).…”

“…The disorder begins with an irregular cell that contains a mutation and then progresses to the largest number of tumor-forming cells. This malignant tumor spreads by penetration of its membrane into adjacent tissues in its advanced stage (2).…”

Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity–Breast Cancer Links

“…Oxidative stress occurs due to an imbalance between antioxidant defenses in the body and production of reactive species, such as reactive oxygen species (ROS) or reaction nitrogen species (RNS) ( 131 ). This stress has been suggested as an important factor in tumor initiation and progression.…”

“…This stress has been suggested as an important factor in tumor initiation and progression. Nitric oxide synthases (NOS), such as endothelial NOS, can generate RNS, and have been shown to modulate processes including inflammation, angiogenesis and metastasis ( 131 ). Human breast cancer cells displayed activation of the EGFR and ERK pathways when treated with nitric oxide, and ultimately showed an increase in invasive potential ( 132 ).…”