Mechanistic Insights and Therapeutic Implications of Endothelial Nitric Oxide Synthase and Reactive Oxygen Species in Breast Cancer.

Abstract

Breast cancer (BC) remains a significant health problem globally, with complex underlying processes that are not fully understood. This study investigates the intricate relationship between endothelial nitric oxide synthase (eNOS) and reactive oxygen species (ROS) in the progressions of BC. Here we examine the essential roles of superoxide (O2·¯), hydrogen peroxide (H₂O₂), and hydroxyl free radicals (OH·) in promoting tumor development, angiogenesis, and metastasis. In addition, this review also analyzes the significant role of eNOS in BC, which highlighting its activation by estrogen and the impact of eNOS gene polymorphisms on cancer risk. Furthermore, we elucidate the mechanisms of eNOS uncoupling, primarily focusing on the deficiency of tetrahydrobiopterin (BH4), the depletion of L-Arginine (L-Arg), and the buildup of asymmetric dimethylarginine (ADMA). This extensive study provides novel insights into the molecular mechanisms connecting oxidative stress and NO signaling in BC. It identifies prospective targets for innovative treatment strategies. Hence, the outcomes of the study may highlight the importance of comprehending the complex balance between eNOS activity and ROS production in the progression of BC. This provides the foundation for further studies and targeted therapies in BC treatment.