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

✍ Scribed by Lucía Policastro; Beatriz Molinari; Fernando Larcher; Patricia Blanco; Osvaldo L. Podhajcer; Cristina S. Costa; Paola Rojas; Hebe Durán

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 152 KB
• Volume: 39
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20001

✦ Synopsis

Abstract

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 (${\rm O}_{\rm 2}^{ \cdot - }$) and hydrogen peroxide (H~2~O~2~) in tumor cell lines with different degrees of malignancy, paired with regard to their origin (PB/CH72T4, PDV/PDVC57, and HBL‐100/MCF‐7). An increase in superoxide dismutase activity and a decrease in the activities of H~2~O~2~‐detoxifying enzymes, as a function of malignancy, coupled with a rise in H~2~O~2~ and a decrease in ${\rm O}_{\rm 2}^{ \cdot - }$ 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 H~2~O~2~ in cell proliferation. Moreover, stable expression of human catalase in MCF‐7 cells inhibited proliferation and also reverted malignant features. We conclude that H~2~O~2~ played 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. © 2004 Wiley‐Liss, Inc.