Abstract

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.

References

• 1. Antico Arciuch V.G., Alippe Y., Carreras M.C., Poderoso J.J.: Mitochondrialkinases in cell signaling: facts and perspectives. Adv. DrugDeliv. Rev., 2009; 61: 1234-1249
  Google Scholar
• 2. Badjatia N., Satyam A., Singh P., Seth A., Sharma A.: Altered antioxidantstatus and lipid peroxidation in Indian patients with urothelialbladder carcinoma. Urol. Oncol., 2010; 28: 360-367
  Google Scholar
• 3. Bednarek I., Sypniewski D., Gawlik N., Galilejczyk A., Goraus K.:The efficiency of silencing expression of the gene coding STAT3transcriptional factor and susceptibility of bladder cancer cells toapoptosis. Contemp. Oncol., 2012; 16: 316-321
  Google Scholar
• 4. Belgorosky D., Langle Y., Prack Mc Cormick B., Colombo L., SandesE., Eijan A.M.: Inhibition of nitric oxide is a good therapeutic targetfor bladder tumors that express iNOS. Nitric Oxide, 2014; 36: 11-18
  Google Scholar
• 5. Chiou C.C., Chang P.Y., Chan E.C.,Wu T.L., Tsao K.C., Wu J.T.: Urinary8-hydroxydeoxyguanosine and its analogs as DNA marker ofoxidative stress: development of an ELISA and measurement in bothbladder and prostate cancers. Clin. Chim. Acta, 2003; 334: 87-94
  Google Scholar
• 6. Degoricija M., Situm M., Korać J., Miljković A., Matić K., ParadzikM., Marinović Terzić I., Jeroncić A., Tomić S., Terzić J.: High NF-κBand STAT3 activity in human urothelial carcinoma: a pilot study.World J. Urol., 2014; 32: 1469-1475
  Google Scholar
• 7. Deniz H., Karakok M., Yagci F., Güldür M.E.: Evaluation of relationshipbetween HIF-1α immunoreactivity and stage, grade, angiogenicprofile and proliferative index in bladder urothelial carcinomas. Int.Urol. Nephrol., 2010; 42: 103-107
  Google Scholar
• 8. Drobna Z., Jaspers I., Thomas D.J., Styblo M.: Differential activationof AP-1 in human bladder epithelial cells by inorganic andmethylated arsenicals. FASEB J., 2003; 17: 67-69
  Google Scholar
• 9. Federico A., Morgillo F., Tuccillo C., Ciardiello F., Loguercio C.:Chronic inflammation and oxidative stress in human carcinogenesis.Int. J. Cancer, 2007; 121: 2381-2386
  Google Scholar
• 10. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., RebeloM., Parkin D.M., Forman D., Bray F.: Cancer incidence and mortalityworldwide: sources, methods and major patterns in GLOBOCAN 2012 Int. J. Cancer, 2015; 136: E359-E386
  Google Scholar
• 11. Fialkow L., Wang Y., Downey G.P.: Reactive oxygen and nitrogenspecies as signaling molecules regulating neutrophil function. FreeRadic. Biol. Med., 2007; 42: 153-164
  Google Scholar
• 12. Gecit I., Aslan M., Gunes M., Pirincci N., Esen R., Demir H., CeylanK.: Serum prolidase activity, oxidative stress, and nitric oxidelevels in patients with bladder cancer. J. Cancer Res. Clin. Oncol.,2012; 138: 739-743
  Google Scholar
• 13. Genestra M.: Oxyl radicals, redox-sensitive signalling cascadesand antioxidants. Cell. Signal., 2007; 19: 1807-1819
  Google Scholar
• 14. Iida K., Itoh K., Maher J.M., Kumagai Y., Oyasu R., Mori Y., ShimazuiT., Akaza H, Yamamoto M.: Nrf2 and p53 cooperatively protectagainst BBN-induced urinary bladder carcinogenesis. Carcinogenesis,2007; 28: 2398-2403
  Google Scholar
• 15. Ioachim E., Michael M., Salmas M., Michael M.M., StavropoulosN.E., Malamou-Mitsi V.: Hypoxia-inducible factors HIF-1α and HIF-2α expression in bladder cancer and their associations with otherangiogenesis-related proteins. Urol. Int., 2006; 77: 255-263
  Google Scholar
• 16. Karlou M., Saetta A.A., Korkolopoulou P., Levidou G., PapanastasiouP., Boltetsou E., Isaiadis D., Pavlopoulos P., Thymara I., Thomas-TsagliE., Patsouris E.: Acivation of extracellular regulated kinases (ERK1/2)predicts poor prognosis in urothelial bladder carcinoma and is notassociated with B-Raf gene mutations. Pathology, 2009; 41: 327-334
  Google Scholar
• 17. Khadjavi A., Barbero G., Destefanis P., Mandili G., Giribaldi G.,Mannu F., Pantaleo A., Ceruti C., Bosio A., Rolle L., Turrini F., FontanaD.: Evidence of abnormal tyrosine phosphorylated proteins inthe urine of patients with bladder cancer: the road toward a newdiagnostic tool? J. Urol., 2011; 185: 1922-1929
  Google Scholar
• 18. Kilic S., Bayraktar N., Beytur A., Ergin H., Bayraktar M., Egri M.:Can the levels of nitric oxide in the urine, serum and tumor tissue beputative markers for bladder cancer. Int. J. Urol., 2006; 13: 1079-1085
  Google Scholar
• 19. Koga F., Yoshida S., Tatokoro M., Kawakami S., Fujii Y., KumagaiJ., Neckers L., Kihara K.: ErbB2 and NFκB overexpression as predictorsof chemoradiation resistance and putative targets to overcome resistancein muscle-invasive bladder cancer. PLoS One, 2011; 6: e27616
  Google Scholar
• 20. Kundu J.K., Surh Y.J.: Emerging avenues linking inflammationand cancer. Free Radic. Biol. Med., 2012; 52: 2013-2037
  Google Scholar
• 21. Lee C.H., Jeon Y.T., Kim S.H., Song Y.S.: NF-κB as a potential moleculartarget for cancer therapy. Biofactors, 2007; 29: 19-35
  Google Scholar
• 22. Levidou G., Saetta A.A., Korkolopoulou P., Papanastasiou P., GiotiK., Pavlopoulos P., Diamantopoulou K., Thomas-Tsagli E., XiromeritisK., Patsouris E.: Clinical significance of nuclear factor (NF)-κBlevels in urothelial carcinoma of the urinary bladder. Virchows Arch.,2008; 452: 295-304
  Google Scholar
• 23. Ma N., Thanan R., Kobayashi H., Hammam O., Wishahi M., ElLeithy T., Hiraku Y., Amro E.K., Oikawa S., Ohnishi S., Murata M., KawanishiS.: Nitrative DNA damage and Oct3/4 expression in urinarybladder cancer with Schistosoma haematobium infection. Biochem.Biophys. Res. Commun., 2011; 414: 344-349
  Google Scholar
• 24. Michaud D.S.: Chronic inflammation and bladder cancer. Urol.Oncol., 2007; 25: 260-268
  Google Scholar
• 25. Murata M., Thanan R., Ma N., Kawanishi S.: Role of nitrative andoxidative DNA damage in inflammation-related carcinogenesis. J.Biomed. Biotechnol., 2012; 2012: 623019
  Google Scholar
• 26. Okamato M., Kawai K., Reznikoff C.A., Oyasu R.: Transformationin vitro of a nontumorigenic rat urothelial cell line by hydrogen peroxide.Cancer Res., 1996; 56: 4649-4653
  Google Scholar
• 27. Opanuraks J., Boonla C., Saelim C., Kittikiwit W., Sumpatanukul P., Honglertsakul C., Tosukhowong P.: Elevated urinary total sialicacid and increased oxidative stress in patients with bladder cancer.Asian Biomed., 2010; 4: 703-710
  Google Scholar
• 28. Pialoux V., Mounier R., Brown A.D., Steinback C.D., RawlingJ.M., Poulin M.J.: Relationship between oxidative stress and HIF-1αmRNA during sustained hypoxia in humans. Free Radic. Biol. Med.,2009; 46: 321-326
  Google Scholar
• 29. Piotrowska A., Iżykowska I., Podhorska-Okołów M., Zabel M.,Dzięgiel P.: Budowa białek z rodziny NF-κB i ich rola w procesie apoptozy.Postępy Hig. Med. Dośw., 2008; 62: 64-74
  Google Scholar
• 30. Przybyszewski W.M., Rzeszowska-Wolny J.: Stres oksydacyjnyw procesach przerostu i kancerogenezy gruczołu sterczowego. PostępyHig. Med. Dośw., 2009; 63: 340-350
  Google Scholar
• 31. Sandes E.O., Faletti A.G., Riveros M.D., Vidal Mdel C., Gimenez L.,Casabe A.R., Eijan A.M.: Expression of inducible nitric oxide synthasein tumoral and non-tumoral epithelia from bladder cancer patients.Nitric Oxide, 2005; 12: 39-45
  Google Scholar
• 32. Sandes E.O., Lodillinsky C., Langle Y., Belgorosky D., Marino L.,Gimenez L., Casabe A.R., Eijan A.M.: Inducible nitric oxide synthaseand PPARγ are involved in bladder cancer progression. J. Urol.,2012; 188: 967-973
  Google Scholar
• 33. Schetter A.J., Heegaard N.H., Harris C.C.: Inflammation and cancer:interweaving microRNA, free radical, cytokine and p53 patchways.Carcinogenesis, 2010; 31: 37-49
  Google Scholar
• 34. Ścibior-Bentkowska D., Czeczot H.: Komórki nowotworowea stres oksydacyjny. Postępy Hig. Med. Dośw., 2009; 63: 58-72
  Google Scholar
• 35. Stępnik M.: Molekularne aspekty toksycznego działania tlenkuazotu. Medycyna Pracy, 2001; 52: 375-381
  Google Scholar
• 36. Wang H., Xi S., Xu Y., Wang F., Zheng Y., Li B., Li X., Zheng Q., SunG.: Sodium arsenite induces cyclooxygenase-2 expression in humanuroepithelial cells through MAPK pathway activation and reactiveoxygen species induction. Toxicol. In Vitro, 2013; 27: 1043-1048
  Google Scholar
• 37. Wang X.J., Sun Z., Chen W., Eblin K.E., Gandolfi J.A., Zhang D.D.:Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonousacid toxicity. Toxicol. Appl. Pharmacol., 2007;225: 206-213
  Google Scholar
• 38. Wiczyńska B., Rolski J.: Terapia celowana. Część I. Mechanizmyprzesyłania sygnałów przy udziale receptorów o aktywności kinazytyrozynowej. Współcz. Onkol., 2007; 11: 331-336
  Google Scholar
• 39. Wojciechowska U., Didkowska J., Zatoński W.: Pięcioletnie prze-życia chorych na nowotwory złośliwe w Polsce. Nowotwory, 2010;60: 122-128
  Google Scholar
• 40. Zhang B., Lu Z., Hou Y., Hu J., Wang C.: The effects of STAT3 andSurvivin silencing on the growth of human bladder carcinoma cells.Tumour Biol., 2014; 35: 5401-5407
  Google Scholar

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