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The mediating role of caspase‐3 protease in the intracellular mechanism of genistein‐induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP
Author(s) -
KumiDiaka James,
Sanderson NaeyhiAelei,
Hall Alexis
Publication year - 2000
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1016/s0248-4900(00)01109-6
Subject(s) - du145 , genistein , lncap , apoptosis , biology , programmed cell death , cancer research , caspase , cell culture , cell growth , caspase 8 , cancer cell , microbiology and biotechnology , endocrinology , cancer , biochemistry , genetics
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.