Hispolon induces apoptosis against prostate DU145 cancer cells via modulation of mitochondrial and STAT3 pathways

Abstract

Hispolon, a bioactive polyphenolic entity extracted from Phellinus linteus, possesses anticancer, antiinflammatory and anti-oxidant properties. Despite the reported therapeutic effects of this natural chemical entity, inhibitory potential of hispolon towards prostate carcinoma DU145 cells and mechanism of its action are yet to be explicated. Deregulated STAT3 pathway performs multifaceted functions in facilitating the development of cancer. Here, we have investigated the mechanism of hispolon by which it exerts its anticancer effects in DU145 cells and whether its anticancer activity is mediated by modulation of STAT3. Our outcomes show that hispolon significantly halted the multiplication of DU145 cells as well as arrested cell cycle at S phase. S phase arrest induced by hispolon was associated with downregulation of cyclin B1, cyclin D1 and CDK4 while up-regulation of p21. Moreover, hispolon treatment leads towards induction of apoptosis in a dose-dependent mode in DU145 cells. Hispolon induced modulation of Bcl-2 family proteins lead towards loss of MMP allowing the discharge of cytochrome c from mitochondrial porin channels which triggered the cascade of caspases ultimately causing cellular death. We further investigated the role of hispolon in mediating deregulated STAT3 pathways in DU145 cells. Hispolon has potential to downregulate the p-STAT3 expression with no effect on total STAT3. Contemporaneously, these results represent that hispolon’s anticancer mechanism of action proceeds via downregulating the phosphorylation of STAT3 and induction of apoptosis via mitochondrial pathway.