Down-regulation of Notch-1 is Associated with Akt and FoxM1 in Inducing Cell Growth Inhibition and Apoptosis in Prostate Cancer Cells

Overview

Journal J Cell Biochem

Specialties Biochemistry
Cell Biology

Date 2010 Jul 27

PMID 20658545

Citations 45

Authors

Zhiwei Wang

Yiwei Li

Aamir Ahmad

Sanjeev Banerjee

Asfar S Azmi

Dejuan Kong

Christine Wojewoda

Lucio Miele

Fazlul H Sarkar

Affiliations

Soon will be listed here.

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.

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