title: Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. zhiweiwang@med.wayne.edu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Banerjee
authors.forename: Asfar S
authors.initials: AS
authors.lastname: Azmi
authors.forename: Dejuan
authors.initials: D
authors.lastname: Kong
authors.forename: Christine
authors.initials: C
authors.lastname: Wojewoda
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D051057:Proto-Oncogene Proteins c-akt