Toyocamycin induces apoptosis via the crosstalk between reactive oxygen species and p38/ERK MAPKs signaling pathway in human prostate cancer PC-3 cells

Background toyocamycin,an antibiotic agent isolated from streptomyces species,has been shown to have anticancer and chemopreventive effects on various cancer cells. until now,toyocamycin-induced apoptosis has not been reported to be involved in the regulation between mitogen-activated protein kinases (mapks) and reactive oxygen species (ros) production. methods cell viability assay,western blot,cell-cycle arrest,annexin v/propidium iodide assay,reactive oxygen species (ros) production,mitochondrial membrane potential and intracellular ca2+ flux were assayed. results we investigated the apoptotic effect of toyocamycin and the underlying molecular mechanism in prostate cancer pc-3 cells. toyocamycin treatment resulted in reduced cell viability of pc-3 cells,but not of non-malignant rwpe-1 cells. toyocamycin enhanced apoptosis,mitochondrial dysfunction,and ros production in pc-3 cells. in addition,mapk proteins were activated upon toyocamycin treatment. the p38 and extracellular signal-regulated kinases (erk) activities were regulated by ros-mediated signaling pathway underlying the toyocamycin-induced apoptosis. pretreatment with n-acetyl-l-cysteine (nac) recovered the toyocamycin-induced mitochondrial dysfunction,ros,and apoptosis. additionally,p38 stimulated ros production and inhibitory effects on erk activation,while erk inhibited the ros production and had no effect on p38 activation. conclusion ros-mediated activation of p38/erk partially contributes to toyocamycin-induced apoptosis,and p38/erk mapks regulate the ros production in pc-3 cells. © 2016 institute of pharmacology,polish academy of sciences