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Tumor Biology

, Volume 35, Issue 5, pp 4137–4145 | Cite as

Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells

  • Tiantian Tian
  • Jisheng Li
  • Bei Li
  • Yawei Wang
  • Meiying Li
  • Daoxin Ma
  • Xiuwen Wang
Research Article

Abstract

Genistein, a major isoflavone constituent in soybeans, has been reported to exhibit multiple anti-tumor effects, such as inducing cell cycle arrest, triggering apoptosis, and inactivating critical signaling pathways in a few human cancer cells. Here, we investigated the anti-tumor effects of genistein on the small-cell lung cancer (SCLC) cell line H446 and the underlying molecular mechanisms. H446 cells were treated with various concentrations of genistein, and experiments including CCK-8 assay, colony formation assay, flow cytometry analysis, wound healing assay, real-time polymerase chain reaction (PCR), western blot analysis, and plasmid transfection were used to investigate the influence of genistein on cell proliferation, migration ability, apoptosis, cell cycle progression, as well as the mRNA and protein alterations of FoxM1 pathway molecules. We found that genistein significantly inhibited the proliferation and migration ability of H446 cell, accompanied by apoptosis and G2/M phase cell cycle arrest. In addition, genistein enhanced the anti-proliferative effect of cisplatin on H446 cells. Importantly, genistein led to attenuation of the FoxM1 protein and down-regulated a series of FoxM1 target genes regulating cell cycle and apoptosis including Cdc25B, cyclin B1, and survivin. In addition, up-regulation of FoxM1 by cDNA transfection prior to genistein treatment could reduce genistein-induced H446 proliferation inhibition. Thus, for the first time, we demonstrated that genistein exerted multiple anti-tumor effects in H446 SCLC cell line at least partly mediated by the down-regulation of FoxM1. FoxM1 has the potential as a novel therapeutic agent in SCLC and is worthy of further study.

Keywords

SCLC Genistein FoxM1 Cell cycle arrest Apoptosis 

Notes

Acknowledgments

This study was funded by the Science and Technology Development Projects of Shandong Province of China (2012GSF11845), Science and Technology Development Projects of Jinan City of Shandong Province (JN100503), Independent Innovation Foundation of Shandong University (2012TS155), and National Natural Science Foundation of China (81372530, 81201934).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Tiantian Tian
    • 1
  • Jisheng Li
    • 1
  • Bei Li
    • 1
  • Yawei Wang
    • 1
  • Meiying Li
    • 1
  • Daoxin Ma
    • 2
  • Xiuwen Wang
    • 1
  1. 1.Department of Medical Oncology, Cancer centerQilu Hospital of Shandong UniversityJinanChina
  2. 2.Department of Hematology, Cancer CenterQilu Hospital of Shandong UniversityJinanChina

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