Phenazine-1-carboxylic acid-induced programmed cell death in human prostate cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway

Phenazine-1-carboxylic acid has extensive pharmacological activity,including antibiotic and immunomodulatory,but the anticancer activity remains unknown. treatment of prostate cancer cell line (du145) with phenazine-1-carboxylic acid stimulated inhibition of cell proliferation in concentration- and time-dependent manner. dual staining confirmed phenazine-1-carboxylic acid stimulated prostate cancer programmed cell death in time-dependent manner. to investigate the exact mechanism,phenazine-1-carboxylic acid-stimulated oxidative stress and mitochondrial-related apoptotic pathway in human prostate cancer cells were examined in this study. phenazine-1-carboxylic acid increased the generation of reactive oxygen species (ros) in prostate cancer cell lines,which triggered the pro-apoptotic jnk signaling. phosphorylated jnk stimulated the depolarization of mitochondrial membrane potential (δψm) and downregulation of anti-apoptotic protein bcl-2 related with the upregulation of pro-apoptotic protein bax. downregulation of anti-apoptotic bcl-2 family protein in corresponding with loss of δψm,stimulate the increased production of cytochrome c and programmed cell death inducing factor (aif) from mitochondria,and ultimately induced the caspase-dependent and caspase-independent programmed cell death. altogether,the present study suggests that phenazine-1-carboxylic acid showed an antitumor activity in prostate cancer cells by reactive oxygen species production and mitochondrial-related apoptotic pathway. the results of the present study offered an insight into the prospective of phenazine-1-carboxylic acid for prostate cancer therapy. © 2016 faculty of health and social sciences,university of south bohemia in ceske budejovice