Modulation of tumor cell proliferation and angiogenesis by catalase treatment inhibits in vivo tumor growth

POLICASTRO, LUCÍA; IBAÑEZ, IRENE L.; PALMIERI, MÓNICA A.; MOLINARI, BEATRIZ; DURÁN H.

Santiago

Congreso; Free Radicals and Antioxidants in Chile. VI Meeting of Society for Free Radical Biology and Medicine (SFRBM) South American Group; 2009

Society for Free Radical Biology and Medicine (SFRBM) South American Group

In view of previous findings that demonstrate a constitutive pro-oxidant state in tumor cells, particularly a high production of H2O2, and that a decrease in H2O2 levels induces a remarkable inhibition of cell proliferation and tumor growth, the aim of this study was to evaluate the mechanisms involved in the in vivo tumor growth inhibition induced by scavenging H2O2. Experimental tumors were induced by inoculating CH72-T4 carcinoma cells in nude mice or by two stage carcinogenesis in SENCAR mice skin. Tumors were treated by subcutaneous inoculation of catalase (1 mg/g body weight) twice a week for 2 weeks. A strong inhibition of tumor growth and a halt in tumor development, associated to a decrease in mitotic index were demonstrated in catalase-treated tumors as compared to control tumors (vehicle-treated or without treatment) in both experimental models. Regarding cell cycle regulatory proteins a decrease in cyclin D1 and an increase in p27KIP1 proteins were detected by immunocytochemistry in treated tumors, in agreement with the results of in vitro studies. Moreover, histologic analysis showed less vascularization and a significant decrease in vascular endothelial growth factor (VEGF) levels, evaluated by immunocytochemistry, in response to catalase treatment. In conclusion, the scavenging of H2O2 would be blocking both signaling pathways related to cell cycle progression and to VEGF expression. Therefore, two relevant processes related to tumor progression, uncontrolled cell proliferation and angiogenesis, would be inhibited by catalase treatment.