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H2O2 inhibits proliferation and mediates suppression of migration via DLC1/RhoA signaling in cancer cells.
- Source :
-
Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2015; Vol. 16 (4), pp. 1637-42. - Publication Year :
- 2015
-
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 H2O2 in regulation of DLC1.<br />Materials and Methods: We treated cells with H2O2 for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays.<br />Results: 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 increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by H2O2 in MDA-MB-231 cells.<br />Conclusions: Our study suggests that H2O2 inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.
- Subjects :
- Apoptosis drug effects
Blotting, Western
Breast metabolism
Breast pathology
Breast Neoplasms metabolism
Breast Neoplasms pathology
Cell Cycle drug effects
Cells, Cultured
Female
Fluorescent Antibody Technique
GTPase-Activating Proteins genetics
Humans
Lung Neoplasms metabolism
Lung Neoplasms pathology
Oxidants pharmacology
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Proteins genetics
Wound Healing drug effects
rhoA GTP-Binding Protein genetics
Breast Neoplasms prevention & control
Cell Movement drug effects
Cell Proliferation drug effects
GTPase-Activating Proteins metabolism
Gene Expression Regulation, Neoplastic drug effects
Hydrogen Peroxide pharmacology
Lung Neoplasms prevention & control
Tumor Suppressor Proteins metabolism
rhoA GTP-Binding Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2476-762X
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Publication Type :
- Academic Journal
- Accession number :
- 25743845
- Full Text :
- https://doi.org/10.7314/apjcp.2015.16.4.1637