Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Apoptosis / physiology
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Bisbenzimidazole / pharmacokinetics
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Carcinoma / drug therapy*
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Carcinoma / enzymology
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Carcinoma / physiopathology
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Caspase 3
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Caspases / drug effects*
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Caspases / metabolism
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Cell Division / drug effects
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Cell Division / physiology
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Cysteine Proteinase Inhibitors / pharmacology
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DNA Fragmentation / drug effects
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DNA Fragmentation / physiology
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Dose-Response Relationship, Drug
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Drug Interactions / physiology
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Fluorescent Dyes / pharmacokinetics
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Genistein / pharmacology*
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Gonadal Steroid Hormones / metabolism
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Gonadal Steroid Hormones / pharmacology
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Humans
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In Situ Nick-End Labeling
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Male
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / enzymology
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Prostatic Neoplasms / physiopathology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / drug effects*
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Tumor Cells, Cultured / enzymology
Substances
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Amino Acid Chloromethyl Ketones
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Antineoplastic Agents
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Cysteine Proteinase Inhibitors
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Fluorescent Dyes
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Gonadal Steroid Hormones
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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Genistein
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CASP3 protein, human
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Caspase 3
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Caspases
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Bisbenzimidazole