Imbalance of antioxidant enzymes in tumor cells and inhibition of proliferation and malignant features by scavenging hydrogen peroxide

LUCÍA POLICASTRO; BEATRIZ MOLINARI; FERNANDO LARCHER; PATRICIA BLANCO; OSVALDO L. PODHAJCER; CRISTINA S. COSTA; PAOLA ROJAS; HEBE DURÁN

MOLECULAR CARCINOGENESIS.

Año: 2004 vol. 39 p. 103 - 113

0899-1987

The aim of this study was to evaluate the endogenous alterations of the antioxidant enzymes in tumor cells and to specifically compensate the resulting changes in the levels of reactive oxygen species (ROS) to control the malignant growth. We determined and compared the activities of antioxidant enzymes and the levels of superoxide anion (O2. ) and hydrogen peroxide (H2O2) in tumor cell lines with different degrees of malignancy, paired considering their origin (PB/CH72T4, PDV/PDVC57 and HBL-100/MCF-7). An increase in superoxide dismutase activity and a decrease in the activities of H2O2-detoxifying enzymes, as a function of malignancy, coupled to a rise in H2O2 and a decrease in O2.  were demonstrated. Treatment of cells with exogenous catalase showed a dose–dependent inhibition of proliferation. This inhibition was also demonstrated in several cell lines of different tissue origin and species, suggesting a general role of H2O2 in cell proliferation. Moreover, stable expression of human catalase in malignant cells (MCF-7) inhibited proliferation and also reverted malignant features. We conclude that H2O2 plays a crucial and general role in the regulation of proliferation and that an endogenous imbalance in antioxidant enzymes could be a relevant event in the carcinogenesis process.