β-Mangostin inhibits the metastatic power of cervical cancer cells attributing to suppression of JNK2/AP-1/Snail cascade.

beta-Mangostin is a natural mangostin with potent anticancer activity against various cancers. In this study, we further explored the anticancer activity of beta-mangostin on cervical cancer cells. beta-Mangostin did not affect cell viability and cell cycle distribution in HeLa and SiHa cells; however, it dose-dependently inhibited the migration and invasion of both the human cervical cancer cell lines. In addition, we observed that beta-mangostin suppressed the expression of integrin alpha V and beta 3 and the downstream focal adhesion kinase/Src signaling. We also found that Snail was involved in the beta-mangostin inhibited cell migration and invasion of HeLa cell. Then, our findings showed that beta-mangostin reduced both nuclear translocation and messenger RNA expression of AP-1 and demonstrated that AP-1 could target to the Snail promoter and induce Snail expression. Kinase cascade analysis and reporter assay showed that JNK2 was involved in the inhibition of AP-1/Snail axis by beta-mangostin in HeLa cells. These results indicate that beta-mangostin can inhibit the mobility and invasiveness of cervical cancer cells, which may attribute to the suppression of both integrin/Src signaling and JNK2-mediated AP-1/Snail axis. This suggests that beta-mangostin has potential antimetastatic potential against cervical cancer cells.