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- Title
Genistein induces G<sub>2</sub>/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells.
- Authors
Zhong Li; Jing Li; Baoqing Mo; Chunyan Hu; Huaqing Liu; Hong Qi; Xinru Wang; Jida Xu
- Abstract
Abstract 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.
- Subjects
THERAPEUTIC use of isoflavones; CANCER cell growth regulation; BREAST cancer; CELL cycle; CARCINOGENICITY testing; CELL lines; WESTERN immunoblotting; PHOSPHORYLATION
- Publication
Cell Biology & Toxicology, 2008, Vol 24, Issue 5, p401
- ISSN
0742-2091
- Publication type
Article
- DOI
10.1007/s10565-008-9054-1