Phenethyl Isothiocyanate-induced Apoptosis in p53-deficient PC-3 Human Prostate Cancer Cell Line Is Mediated by Extracellular Signal-regulated Kinases

摘要: Previous studies have suggested that p53 is required for apoptosis induction by phenethyl isothiocyanate (PEITC), which a highly promising cancer chemopreventive agent. Here, we report not PEITC-induced in the PC-3 human prostate cell line and mediated extracellular signal-regulated kinases (ERK1/2). Exposure of cells to an apoptosis-inducing concentration PEITC (10 μm) resulted rapid sustained activation ERK1/2 was evident as early 1 h after treatment persisted duration experiment (24-h exposure). The PEITC-mediated associated with increase phosphorylation its substrate Elk-1 at Ser383. well abolished presence mitogen-activated protein/ERK kinase (a upstream ERK1/2) inhibitor PD98059. 10 μm also time-dependent p38 protein increased activating transcription factor 2 Thr71. Even though abrogated specific SB202190, inhibition did prevent apoptosis. In contrast previous reports other cellular systems, c-Jun NH2-terminal were activated carcinoma line. conclusion, results present study indicate essential ERKs. Thus, it seems reasonable postulate may be effective against tumors normal mutant p53.