H2O2 scavenging inhibits G1/S transition by increasing nuclear levels of p27KIP1

The aim of the present study was to evaluate cell cycle regulation by scavenging H2O2 in tumor cells. A significant arrest in the G1 phase of the cell cycle was demonstrated in CH72-T4 carcinoma cells exposed to catalase, associated with a decrease in cyclin D1 and an increase in the CDK inhibitory protein p27KIP1. Moreover, we found a differential intracellular distribution of p27KIP1, which remained in the nucleus after catalase treatment. In vivo experiments showed an increase in nuclear levels of p27KIP1 associated with the inhibition of tumor growth by H2O2 scavenging, confirming in vitro results. To conclude, H2O2 scavenging may induce cell cycle arrest through the modulation of cyclin D1 and p27KIP1 levels and nuclear localization of p27KIP1. To our knowledge, this is the first report that demonstrates that the modulation of ROS alters the intracellular localization of a key regulatory protein of G1/S transition.