Accumulating evidence demonstrated that
alteronol, a novel compound that has a similar structure with
paclitaxel, exerts anticancer effects against diversified
tumors. However, whether
alteronol induces autophagy and the relationship between its anticancer effects and autophagy in
melanoma remains elusive. In this study, we show that
alteronol induces not only anti-proliferation activity and apoptosis but also autophagy in A375 and UACC62 cells. In addition,
alteronol inhibits A375 and UACC62 cells invasion and migration by preventing the epithelial-mesenchymal transition (EMT). Blocking autophagy enhances
alteronol-induced apoptosis and anti-EMT effects in vitro and in vivo. Mechanistically, we find that
alteronol significantly inhibits Akt/mTOR and TGFβ/Smad3 pathways, and co-treatment with autophagy inhibitor 3-MA further potentiate these effects. Our results suggest that
alteronol induces cyto-protective autophagy in
melanoma cells through inhibition of Akt/mTOR pathway, thus attenuates apoptosis and promotes
melanoma cell EMT through TGF-β/Smad3 pathway. Combination with
alteronol and autophagy inhibitor 3-MA may be a potential treatment for
melanoma as it not only significantly inhibited
tumor growth but also suppressed
tumor invasion and migration as anti-
metastasis agent.