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The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation

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 inves...

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Autores principales: Kang, Soouk, Kim, Jong-Eun, Song, Nu Ry, Jung, Sung Keun, Lee, Mee Hyun, Park, Jun Seong, Yeom, Myeong-Hun, Bode, Ann M., Dong, Zigang, Lee, Ki Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138097/
https://www.ncbi.nlm.nih.gov/pubmed/25137374
http://dx.doi.org/10.1371/journal.pone.0104305
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author Kang, Soouk
Kim, Jong-Eun
Song, Nu Ry
Jung, Sung Keun
Lee, Mee Hyun
Park, Jun Seong
Yeom, Myeong-Hun
Bode, Ann M.
Dong, Zigang
Lee, Ki Won
author_facet Kang, Soouk
Kim, Jong-Eun
Song, Nu Ry
Jung, Sung Keun
Lee, Mee Hyun
Park, Jun Seong
Yeom, Myeong-Hun
Bode, Ann M.
Dong, Zigang
Lee, Ki Won
author_sort Kang, Soouk
collection PubMed
description 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.
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spelling pubmed-41380972014-08-20 The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation Kang, Soouk Kim, Jong-Eun Song, Nu Ry Jung, Sung Keun Lee, Mee Hyun Park, Jun Seong Yeom, Myeong-Hun Bode, Ann M. Dong, Zigang Lee, Ki Won PLoS One Research Article 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. Public Library of Science 2014-08-19 /pmc/articles/PMC4138097/ /pubmed/25137374 http://dx.doi.org/10.1371/journal.pone.0104305 Text en © 2014 Kang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kang, Soouk
Kim, Jong-Eun
Song, Nu Ry
Jung, Sung Keun
Lee, Mee Hyun
Park, Jun Seong
Yeom, Myeong-Hun
Bode, Ann M.
Dong, Zigang
Lee, Ki Won
The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation
title The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation
title_full The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation
title_fullStr The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation
title_full_unstemmed The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation
title_short The Ginsenoside 20-O-β-D-Glucopyranosyl-20(S)-Protopanaxadiol Induces Autophagy and Apoptosis in Human Melanoma via AMPK/JNK Phosphorylation
title_sort ginsenoside 20-o-β-d-glucopyranosyl-20(s)-protopanaxadiol induces autophagy and apoptosis in human melanoma via ampk/jnk phosphorylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138097/
https://www.ncbi.nlm.nih.gov/pubmed/25137374
http://dx.doi.org/10.1371/journal.pone.0104305
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