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Down‐regulation of Notch‐1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells
Author(s) -
Wang Zhiwei,
Li Yiwei,
Ahmad Aamir,
Banerjee Sanjeev,
Azmi Asfar S.,
Kong Dejuan,
Wojewoda Christine,
Miele Lucio,
Sarkar Fazlul H.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22770
Subject(s) - notch signaling pathway , foxm1 , protein kinase b , apoptosis , microbiology and biotechnology , cancer research , pi3k/akt/mtor pathway , notch 1 , cell growth , viability assay , biology , signal transduction , prostate cancer , cell , cell cycle , chemistry , cancer , biochemistry , genetics
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. © 2010 Wiley‐Liss, Inc.