Inhibition of tobacco smoke-induced bladder MAPK activation and epithelial-mesenchymal transition in mice by curcumin.

Tobacco smoke (TS) has been shown to cause bladder cancer. Epithelial-mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. MAPK pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study we investigated the effects of TS on MAPK pathway activation and EMT alterations in the bladder of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12 weeks resulted in activation of ERK1/2, JNK, p38 and ERK5 MAPK pathways as well as AP-1 proteins in bladder. TS reduced mRNA and protein expression levels of epithelial markers E-cadherin and ZO-1, while mRNA and protein expression levels of the mesenchymal markers vimentin and N-cadherin were increased. Curcumin treatment effectively attenuated TS-triggered activation of ERK1/2, JNK and p38 MAPK pathways, AP-1 proteins and EMT alterations in bladder tissue. These results suggest the protective effects of curcumin in TS-induced MAPK activation and EMT, thus providing new insights into the chemoprevention of TS-associated bladder cancer.