Anticancer effects of
dendropanoxide (DP) newly isolated from leaves and stem of Dendropanax morbifera Leveille were firstly investigated in this study. DP inhibited cell proliferation and induced apoptosis in dose- and time-dependent manner in MG-63 human
osteosarcoma cells, which was dependent on the release of
cytochrome c to the cytosol and the activation of
caspases. Moreover, the DP-treated cells exhibited autophagy, as characterized by the punctuate patterns of
microtubule-associated protein 1 light chain 3 (LC3) by confocal microscopy and the appearance of autophagic vacuoles by MDC staining. The expression levels of ATG7,
Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of autophagy by
3-methyladenine (3-MA) and
wortmannin (Wort) significantly enhanced DP-induced apoptosis. DP treatment also caused a time-dependent increase in
protein levels of
extracellular signal-regulated kinase 1 and 2 (ERK1/2), and inhibition of ERK1/2 phosphorylation with
U0126 resulted in a decreased DP-induced autophagy that was accompanied by an increased apoptosis and a decreased cell viability. These results indicate a cytoprotective function of autophagy against DP-induced apoptosis and suggest that the combination of DP treatment with autophagy inhibition may be a promising strategy for human
osteosarcoma control. Taken together, this study demonstrated for the first time that DP could induce autophagy through ERK1/2 activation in human
osteosarcoma cells and autophagy inhibition enhanced DP-induced apoptosis.