A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with NADPH Oxidases, Angiogenesis, and Apoptosis

Abstract

Oxidative stress refers to elevated reactive oxygen species (ROS) levels, and NADPH oxidases (NOXs), which are one of the most important sources of ROS. Oxidative stress plays important roles in the etiologies, pathological mechanisms, and treatment strategies of vascular diseases. Additionally, oxidative stress affects mechanisms of carcinogenesis, tumor growth, and prognosis in malignancies. Nearly all solid tumors show stimulation of neo-vascularity, termed angiogenesis, which is closely associated with malignant aggressiveness. Thus, cancers can be seen as a type of vascular disease. Oxidative stress-induced functions are regulated by complex endogenous mechanisms and exogenous factors, such as medication and diet. Although understanding these regulatory mechanisms is important for improving the prognosis of urothelial cancer, it is not sufficient, because there are controversial and conflicting opinions. Therefore, we believe that this knowledge is essential to discuss observations and treatment strategies in urothelial cancer. In this review, we describe the relationships between members of the NOX family and tumorigenesis, tumor growth, and pathological mechanisms in urological cancers including prostate cancer, renal cell carcinoma, and urothelial cancer. In addition, we introduce natural compounds and chemical agents that are associated with ROS-induced angiogenesis or apoptosis.

Keywords: NADPH oxidases; angiogenesis; apoptosis; reactive oxygen species; urological cancers.

Figure 1

Oxidative stress is defined as an imbalance between the cellular production of reactive oxygen species (ROS) and antioxidants (AOX). Under natural conditions, the production of pro- and antioxidants is in a stable equilibrium. Excessive ROS production or depletion of antioxidants can cause oxidative stress, which may damage cellular lipids, proteins, and DNA, with the latter leading to chromosomal instability and gene mutations.