Abstract
We assessed the catalase bioactivity and hydrogen peroxide (H&sub2;O&sub2;) production rate in human breast cancer (HBC) cell lines and compared these with normal human breast epithelial (HBE) cells. We observed that the bioactivity of catalase was decreased in HBC cells when compared with HBE cells. This was also accompanied by an increase in H&sub2;O&sub2; steady-state levels in HBC cells. Silencing the catalase gene led to a further increase in the steady-state level of H&sub2;O&sub2; which was also accompanied by an increase in growth rate of HBC cells. Catalase activity was up regulated on treatment with superoxide (O&sub2;⁻) scavengers such as pegylated SOD (PEG-SOD, indicating inhibition of catalase by the increased O&sub2;⁻ produced by HBC cells. Transfection of either catalase or glutathione peroxidase to HBC cells decreased intracellular H&sub2;O&sub2; levels and led to apoptosis of these cells. The H&sub2;O&sub2; produced by HBC cells inhibited PP2A activity accompanied by increased phosphorylation of Akt and ERK1/2. The importance of catalase bioactivity in breast cancer was further confirmed as its bioactivity was also decreased in human breast cancer tissues when compared to normal breast tissues. We conclude that inhibition of catalase bioactivity by O&sub2;⁻ leads to an increase in steady-state levels of H&sub2;O&sub2; in HBC cells, which in turn inhibits PP2A activity, leading to phosphorylation of ERK 1/2 and Akt and resulting in HBC cell proliferation.