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

  • Ma, Long (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Zhu, Wen-Zhen (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Liu, Ting-Ting (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Fu, Hui-Ling (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Liu, Zhao-Jun (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Yang, Bing-Wu (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Song, Tai-Yu (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University) ;
  • Li, Guo-Rong (Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University)
  • Published : 2015.03.09

Abstract

Background: RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whether individual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers have shown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The present study was designed to explore the role of $H_2O_2$ in regulation of DLC1. Materials and Methods: We treated cells with $H_2O_2$ for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays. Results: $H_2O_2$ downregulated cyclin D1 and cyclin E to inhibit proliferation, and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, $H_2O_2$ increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by $H_2O_2$ in MDA-MB-231 cells. Conclusions: Our study suggests that $H_2O_2$ inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.

Keywords

$H_2O_2$;proliferation;deleted in liver cancer 1;RhoA;migration

Acknowledgement

Supported by : National Natural Science Foundation of China

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