Inhibition of STAT 3 signalling contributes to the antimelanoma action of atractylenolide II

Our previous studies showed that atractylenolide II ( AT ‐ II ) has antimelanoma effects in B 16 melanoma cells. In this study, we investigated the involvement of STAT 3 signalling in the antimelanoma action of AT ‐ II . Daily administration of AT ‐ II (12.5, 25 mg/kg, i.g.) for 14 days significantly inhibited tumor growth in a B 16 xenograft mouse model and inhibited the activation/phosphorylation of STAT 3 and S rc in the xenografts. In B 16 and A 375 cells, AT ‐ II (20, 40  μ m ) treatment for 48 h dose‐dependently reduced protein expression levels of phospho‐ STAT 3, phospho‐ S rc, as well as STAT 3‐regulated M cl‐1 and B cl‐x L . Overexpression of a constitutively active variant of STAT 3, STAT 3 C in A 375 cells diminished the antiproliferative and apoptotic effects of AT ‐ II . These data suggest that inhibition of STAT 3 signalling contributes to the antimelanoma action of AT ‐ II . Our findings shed new light on the mechanism of action underlying the antimelanoma effects of AT ‐ II and provide further pharmacological basis for developing AT ‐ II as a novel melanoma chemopreventive/chemotherapeutic agent.