Genistein induces G2/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells
| Autor: | Zhong Li, Jing Li, Jida Xu, Hong Qi, Chunyan Hu, Xinru Wang, Baoqing Mo, Huaqing Liu |
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| Rok vydání: | 2008 |
| Předmět: |
G2 Phase
MAPK/ERK pathway Cell cycle checkpoint Health Toxicology and Mutagenesis Genistein Biology Toxicology chemistry.chemical_compound Cell Line Tumor Humans Phosphorylation Protein Kinase Inhibitors Flavonoids Mitogen-Activated Protein Kinase 1 Cyclin-dependent kinase 1 Mitogen-Activated Protein Kinase 3 Dose-Response Relationship Drug Cell growth Cell Cycle food and beverages Cell Biology Cell cycle Flow Cytometry Molecular biology Enzyme Activation Proto-Oncogene Proteins c-raf chemistry Cell culture Cancer cell Cell Division |
| Zdroj: | Cell Biology and Toxicology. 24:401-409 |
| ISSN: | 1573-6822 0742-2091 |
| DOI: | 10.1007/s10565-008-9054-1 |
| Popis: | Genistein is an isoflavonoid present in soybeans that exhibits anti-carcinogenic effect. Several studies have shown that genistein can trigger G2/M cell cycle arrest and inhibit cell growth in human breast cancer cells. In the present study, we assessed the role of MEK-ERK cascade in regulation of genistein-mediated G2/M cell cycle arrest in the hormone-independent cell line MDA-MB-231. Flow cytometric analysis showed that treatment of MDA-MB-231 cells with genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle, with a parallel depletion of the percentage of cells in G0/G1. Genistein-mediated G2/M arrest was associated with a decrease in the protein levels of Cdk1, cyclinB1, and Cdc25C as determined by Western blot analysis. Genistein induced a slow and stable activation of phosphorylated ERK1/2 in a concentration- and time-dependent manner in MDA-MB-231 cells. MEK1/2-specific inhibitor PD98059 blocked genistein-induced activation of ERK1/2 and markedly attenuated genistein-induced G2/M arrest. Furthermore, genistein induced the expression of Ras and Raf-1 protein. Genistein also up-regulated steady-state levels of both c-Jun and c-Fos. PD98059 did not depress genistein-induced up-regulation of Ras and Raf-1 protein. However, it markedly blocked genistein-induced up-regulation of c-Jun and c-Fos. These results suggest that the Ras/MAPK/AP-1 signal pathway may be involved in genistein-induced G2/M cell cycle arrest in MDA-MB-231 breast cancer cells. |
| Databáze: | OpenAIRE |
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