The role of oxidative stress in bladder cancer

The review of the knowledge concerning the impact of oxidative and nitrosative stress on signaling pathways and transcription factors involved in the formation of bladder cancer was prepared. In the industrialized countries, bladder cancer is the fourth most frequently occurring malignant tumors. Recent studies indicate the involvement of oxidative and nitrosative stress in the formation and development of this disease. Red-ox disorders are characteristic for both, the initiation and progression of bladder cancer. There are observed changes in the activity of transcription factors, such as nuclear factor NF-kB; transcription factors: AP-1, Nrf2 and STAT3 and hypoxia-inducible factor HIF-1α. In addition, studies indicate a role for oxidative stress in the regulation of MAPK cascade and its involvement in carcinogenesis consisting bladder. Examples of kinases belonging to the MAPK family are ERK kinases, which expression is proportional to the severity and malignant of bladder cancer. Nitric oxide also plays an important role in tumor biology. Overproduction of NO can both inhibit and promote tumor growth, depending on its concentration, duration of action and tumor microenvironment. Numerous studies show that the bladder cancer is characterized by an intensified production of NO. Reactive forms of nitrogen, similar to oxygen free radicals, could cause oxidative and nitrosative damage to DNA and have capacity to post-translational modification of proteins. In contrast to the ROS, which overproduction result from exposure to carcinogenic xenobiotic, nitrogen oxide in high level is produced during inflammation. Sustained iNOS activity therefore plays an important role in carcinogenesis associated with the inflammatory response, characteristic also for bladder cancer.