title: Dendropanoxide induces autophagy through ERK1/2 activation in MG-63 human osteosarcoma cells and autophagy inhibition enhances dendropanoxide-induced apoptosis.
abstract: 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.
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan, South Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan, South Korea.
authors.forename: Kyoung-Sook
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan, South Korea.
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: An
authors.affiliation: Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Kyunggi-Do, South Korea.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan, South Korea.
authors.forename: Hyung-In
authors.initials: HI
authors.lastname: Moon
authors.affiliation: College of Natural Resources and Life Science, Dong-A University, Busan, South Korea.
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D014315:Triterpenes; C546793:dendropanoxide; C025946:3-methyladenine; D000225:Adenine