H2O2 Inhibits Proliferation and Mediates Suppression of Migration via DLC1/RhoA Signaling in Cancer Cells

Abstract

<b>Background:</b> RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whetherindividual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers haveshown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The presentstudy was designed to explore the role of H2O2 in regulation of DLC1. Materials and <br/><b>Methods</b>: We treated cells withH2O2 for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescencestaining and wound healing assays. <br/><b>Results</b>: H2O2 downregulated cyclin D1 and cyclin E to inhibit proliferation,and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, H2O2 increasedexpression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration werealso suppressed by H2O2 in MDA-MB-231 cells. <br/><b>Conclusions</b>: Our study suggests that H2O2 inhibits proliferationthrough modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibersvia DLC1/RhoA signaling.