The DNA topoisomerase I inhibitor β-lapachone, the product of a tree from South America, is known to exhibit various biological properties, the mechanisms of which are poorly understood. We investigated the effects of β-lapachone on the growth of human prostate epithelial cells. Upon treatment with β-lapachone, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin and DNA fragmentation. The apoptotic effects of β-lapachone were associated with marked induction of p53 phosphorylation and Bax protein without altering the expression of p53 and Bcl-2 protein. In addition, the proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase, β-catenin and Rad51, which are hallmarks of apoptosis, were observed, and Western blotting demonstrated that processing/activation of caspases release cytochrome c from the mitochondria into the cytosol and accompany the generation of β-lapachone-mediating apoptotic cell death. However, β-lapachone did not affect the levels of c-IAP family proteins. The present results suggest that apoptotic signals evoked by β-lapachone in human prostate epithelial cells may converge caspases activation through up-regulation of phosphorylation of p53 and Bax rather than down-regulation of c-IAPs family.

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