Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 112, Issue 1, Pages 78-88Publisher
WILEY
DOI: 10.1002/jcb.22770
Keywords
NOTCH-1; PROSTATE CANCER; CELL GROWTH; APOPTOSIS; Akt; FoxM1
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Funding
- Department of Defense [W81XWH-08-1-0196]
- National Cancer Institute, NIH [5R01CA083695, 1R01CA101870]
- NATIONAL CANCER INSTITUTE [R01CA101870, R01CA083695] Funding Source: NIH RePORTER
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Although many studies have been done to uncover the mechanisms by which down-regulation of Notch-1 exerts its anti-tumor activity against a variety of human malignancies, the precise molecular mechanisms remain unclear. In the present study, we investigated the cellular consequence of Notch-1 down-regulation and also assessed the molecular consequence of Notch-1-mediated alterations of its downstream targets on cell viability and apoptosis in prostate cancer (PCa) cells. We found that the down-regulation of Notch-1 led to the inhibition of cell growth and induction of apoptosis, which was mechanistically linked with down-regulation of Akt and FoxM1, suggesting for the first time that Akt and FoxM1 are downstream targets of Notch-1 signaling. Moreover, we found that a natural agent (genistein) originally discovered from soybean could cause significant reduction in cell viability and induced apoptosis of PCa cells, which was consistent with down-regulation of Notch-1, Akt, and FoxM1. These results suggest that down-regulation of Notch-1 by novel agents could become a newer approach for the prevention of tumor progression and/or treatment, which is likely to be mediated via inactivation of Akt and FoxM1 signaling pathways in PCa. J. Cell. Biochem. 112: 78-88, 2011. (C) 2010 Wiley-Liss, Inc.
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