Effects of Reactive Oxygen Species on Cell Proliferation and Death in HeLa Cells and Its MDR1-Overexpressing Derivative Cell Line

Abstract

In this paper, the effects of H₂O₂, a typical reactive oxygen species (ROS), on cell proliferation or death were examined using the human cervical carcinoma cell line HeLa and its MDR1-overexpressing subline, Hvr100-6, which was established by stepwise exposure to vinblastine. It was confirmed that the growth of HeLa cells was enhanced by H₂O₂ at relatively low concentrations in a concentration-dependent manner, and the growth enhancement was suppressed by antioxidants. Doxorubicin and daunorubicin also enhanced the growth of HeLa cells at concentrations lower than IC₅₀ values, and the antioxidants suppressed this effect, being consistent with the fact that both anticancer drugs generate ROS. The growth enhancement by H₂O₂ or doxorubicin and daunorubicin was not observed in Hvr100-6 cells. In addition, it was suggested that antioxidants had no effect on MDR1 mRNA expression in HeLa and Hvr100-6 cells, and thereby hardly reverse multidrug resistance in tumor cells.