Volume 92, Issue 8-9 p. 595-604

The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP

James Kumi-Diaka

Corresponding Author

James Kumi-Diaka

Department of Biology, College of Liberal Arts and Sciences, Davie campus, Florida Atlantic University, 2912 College Avenue, Davie, FL 33314, USA

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Naeyhi-Aelei Sanderson

Naeyhi-Aelei Sanderson

Department of Biology, College of Liberal Arts and Sciences, Davie campus, Florida Atlantic University, 2912 College Avenue, Davie, FL 33314, USA

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Alexis Hall

Alexis Hall

Department of Biology, College of Liberal Arts and Sciences, Davie campus, Florida Atlantic University, 2912 College Avenue, Davie, FL 33314, USA

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First published: 01 February 2012
Citations: 54

Abstract

Summry— A series of in vitro studies were carried out to investigate genistein-induced cell death, and the nature of cell death, in two human prostate cancer cell lines (LNCaP and Du145), and the possible involvement of caspase-3 protease in genistein-induced apoptosis in the target cells. The major findings of these studies are: i) genistein inhibits growth and proliferation of both LNCaP and DU145 cells via apoptosis mainly, and necrosis at higher concentrations; ii) genistein induces activation and expression of caspase-3 (CPP32) in both target cells; iii) genistein-induced apoptosis and CPP32 activation could be significantly inhibited by the caspase-3 inhibitor, z-VAD-fmk (N—benzyloxycarbonyl-Val-Asp-fluoromethyl—ketone), thus confirming a mediator role of CPP32 in the genistein-induced apoptotic pathway in the target cells. The potency of most known chemopreventive drugs for cancer is due to induction of apoptosis in solid tumors (Thompson, Science 267 (1995) 1456; Gurney et al., Science 288 (2000) 283). Inevitably, agents that increase transcription of caspase-3 protease could reinforce cell death via CPP32-mediated apoptosis. In this regard, genistein may find an application in the treatment of human prostate carcinoma, independently of hormone sensitivity.

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