Cell Biology and Toxicology

, 24:401 | Cite as

Genistein induces G2/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells

  • Zhong LiEmail author
  • Jing Li
  • Baoqing Mo
  • Chunyan Hu
  • Huaqing Liu
  • Hong Qi
  • Xinru Wang
  • Jida Xu


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.


Genistein Cell cycle arrest ERK1/2 pathway Breast cancer 



We thank Drs. Ruiwen Zhang, Donald L. Hill, and Hui Wang for help in the preparation of the manuscript. This work was supported by grant 30271122 from National Natural Science Foundation of China, grant BK2002027 from Natural Science Foundation of Jiangsu Province (to Z. Li).


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Zhong Li
    • 1
    Email author
  • Jing Li
    • 2
  • Baoqing Mo
    • 2
  • Chunyan Hu
    • 2
  • Huaqing Liu
    • 1
  • Hong Qi
    • 1
  • Xinru Wang
    • 1
  • Jida Xu
    • 2
  1. 1.The Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of ToxicologyNanjing Medical UniversityNanjingChina
  2. 2.Department of Nutrition & Food ScienceNanjing Medical UniversityNanjingChina

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