title: The ginsenoside 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol induces autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation.
abstract: Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1, called 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits anticancer properties. However, the chemotherapeutic effects and molecular mechanisms behind GPD action in human melanoma have not been previously investigated. Here we report the anticancer activity of GPD and its mechanism of action in melanoma cells. GPD, but not its parent compound Rb1, inhibited melanoma cell proliferation in a dose-dependent manner. Further investigation revealed that GPD treatment achieved this inhibition through the induction of autophagy and apoptosis, while Rb1 failed to show significant effect at the same concentrations. The inhibitory effect of GPD appears to be mediated through the induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings suggest that GPD suppresses melanoma growth by inducing autophagic cell death and apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be developed as a chemotherapeutic agent for the treatment of human melanoma.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
authors.forename: Soouk
authors.initials: S
authors.lastname: Kang
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Nu Ry
authors.initials: NR
authors.lastname: Song
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America; Functional Food Resources Research Group, Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
authors.forename: Mee Hyun
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea.
authors.forename: Myeong-Hun
authors.initials: MH
authors.lastname: Yeom
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea; Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005894:Panax / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; D048031:JNK Mitogen-Activated Protein Kinases; D058570:TOR Serine-Threonine Kinases; C442759:ginsenoside Rb1; C112772:ginsenoside compound K; C546842:MTOR protein, human