β‐mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP‐2 and MMP‐9 expression and activating the ERK and JNK pathways

<jats:title>Abstract</jats:title><jats:p>β‐mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β‐mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β‐mangostin did not induce cytotoxicity in human HCC cells (SK‐Hep‐1, Huh‐7 and HA22T/VGH cells). β‐mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β‐mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)‐2 and MMP‐9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP‐2/‐9 and invasion by β‐mangostin treatment in Huh‐7 cells. In addition, β‐mangostin effectively restored the protein levels and transcription activity of MMP‐2 and MMP‐9 in siERK or siJNK‐transfected Huh‐7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of β‐mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.</jats:p>