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

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 (O2*-) and hydrogen peroxide (H2O2) 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 H2O2-detoxifying enzymes, as a function of malignancy, coupled with 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 MCF-7 cells inhibited proliferation and also reverted malignant features. We conclude that H2O2 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.

RA Differentiation Enhances Dopaminergic Features, Changes Redox Parameters, and Increases Dopamine Transporter Dependency in 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells

“…The oxidative environment of the undifferentiated cells could be explained by its proliferative profile since H 2 O 2 is fundamental for cellular growth (Policastro et al 2004;Sies 2014). …”

The Effect of Rapamycin on Oxidative Stress in MCF-7 and MDA MB-231 Human Breast Cancer Cell Lines

“…Hence, the increase in the ROS level by these anticancer drugs pushes the cancer cells beyond the breaking point where cellular organelles and DNA are damaged and the cell undergoes apoptosis. Thus, a recurrence of the tumor after therapy likely results from a subset of cells that have developed the ability to overcome oxidative damage (14).…”

Synthesis, Characterization, and the Antioxidative Activity of 4-{[(3,4-Dimethyl pyrrole-2-carbonyl)hydrazono](phenyl)methyl}-3-methyl-1-phenylpyrazol-5-ol and Its Zinc(II), Copper(II), Nickel(II) Complexes

“…1) Cumulative information has been proved that the oxidation induced by ROS can result in cell membrane disintegration, membrane protein damage and DNA mutation, which can further initiate or propagate the development of many diseases, such as cancer, liver injury and cardiovascular disease. 2,3) Catalase, superoxide dismutase, glutathione and uric acid are examples of antioxidants produced by organisms under normal conditions as parts of a defense system against ROS-mediated cellular injury.…”