Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Figure 1

ROS generation and increased antioxidants in PCa cells. The generation of ROS is mainly dependent on both exogenous and endogenous sources. Exogenous sources comprise hypoxia, growth factors, androgen, inflammation, radiation, and chemotherapy; endogenous sources of ROS mainly include mitochondrial dysfunction, the activity of NADPH oxidases, and p66Shc. When ROS levels rise, PCa cells can responsively modulate Keap1/Nrf2/ARE axis and upregulate antioxidants to prevent their accumulation and deleterious actions. Increased antioxidants involve SOD, CAT, Trx, and GSH, whereas antioxidant defenses cannot neutralize elevated ROS, thus disrupting the redox homeostasis. Eventually, a new state called as oxidative stress arises. OXPHOS: oxidative phosphorylation; Keap1: Kelch-like ECH-associated protein 1; ARE: antioxidant responsive element; NOXs: NADPH oxidases; SOD: superoxide dismutase; CAT: catalase; Trx: thioredoxin; GSH: glutathione. Dash arrows indicate the class of ROS, while filled arrows indicate direct or indirect actions.