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

Abstract β‐Mangostin is a natural mangostin with potent anticancer activity against various cancers. In this study, we further explored the anticancer activity of β‐mangostin on cervical cancer cells. β‐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 β‐mangostin suppressed the expression of integrin αV and β3 and the downstream focal adhesion kinase/Src signaling. We also found that Snail was involved in the β‐mangostin inhibited cell migration and invasion of HeLa cell. Then, our findings showed that β‐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 β‐mangostin in HeLa cells. These results indicate that β‐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 β‐mangostin has potential antimetastatic potential against cervical cancer cells.