Pharmaceutical Research

, Volume 27, Issue 6, pp 1159–1168 | Cite as

FoxM1 is a Novel Target of a Natural Agent in Pancreatic Cancer

  • Zhiwei Wang
  • Aamir Ahmad
  • Sanjeev Banerjee
  • Asfar Azmi
  • Dejuan Kong
  • Yiwei Li
  • Fazlul H. Sarkar
Research Paper



Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and/or treatment are urgently needed. Genistein has been found to be responsible for lowering the rate of pancreatic cancer. However, the molecular mechanisms by which genistein elicits its effects on pancreatic cancer cells has not been fully elucidated. Therefore, the purpose of the current study was to elucidate the anti-cancer mechanism(s) of genistein.


Multiple molecular techniques, such as Real-time RT-PCR, Western blot analysis, invasion assay, immunofluorescence assay, gene transfection, MTT assay, and Histone/DNA ELISA, were used.


We found that genistein inhibited cell growth accompanied by induction of apoptosis with concomitant attenuation of FoxM1 and its downstream genes, such as survivin, cdc25a, MMP-9, and VEGF, resulting in the inhibition of pancreatic cancer cell invasion. We also found that down-regulation of FoxM1 by siRNA prior to genistein treatment resulted in enhanced cell growth inhibition and induction of apoptosis.


This is the first report showing the molecular role of FoxM1 in mediating the biological effects of genistein in pancreatic cancer cells, suggesting that FoxM1 could be a novel target for the treatment of pancreatic cancer.


FoxM1 genistein invasion pancreatic cancer proliferation 



Enzyme-linked Immunosorbent Assay


Forkhead box protein M1


Matrix metalloproteinases


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Reverse transcription-PCR


Vascular endothelial growth factor



This work was partly funded by grants from the National Cancer Institute, NIH (R01CA131151 and R01CA132794) to F.H.S. We also sincerely thank both Puschelberg and Guido foundation for their generous contributions to our research.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Zhiwei Wang
    • 1
  • Aamir Ahmad
    • 1
  • Sanjeev Banerjee
    • 1
  • Asfar Azmi
    • 1
  • Dejuan Kong
    • 1
  • Yiwei Li
    • 1
  • Fazlul H. Sarkar
    • 1
  1. 1.Department of Pathology, Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA

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