Pharmaceutical Research

, Volume 27, Issue 6, pp 1159–1168

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

Authors

  • Zhiwei Wang
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
  • Aamir Ahmad
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
  • Sanjeev Banerjee
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
  • Asfar Azmi
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
  • Dejuan Kong
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
  • Yiwei Li
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
    • Department of Pathology, Karmanos Cancer InstituteWayne State University School of Medicine
Research Paper

DOI: 10.1007/s11095-010-0106-x

Cite this article as:
Wang, Z., Ahmad, A., Banerjee, S. et al. Pharm Res (2010) 27: 1159. doi:10.1007/s11095-010-0106-x

ABSTRACT

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

KEY WORDS

FoxM1genisteininvasionpancreatic cancerproliferation

ABBREVIATIONS

ELISA

Enzyme-linked Immunosorbent Assay

FoxM1

Forkhead box protein M1

MMPs

Matrix metalloproteinases

MTT

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

RT-PCR

Reverse transcription-PCR

VEGF

Vascular endothelial growth factor

Copyright information

© Springer Science+Business Media, LLC 2010