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Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo

Autophagy can result in cellular adaptation, as well as cell survival or cell death. Modulation of autophagy is increasingly regarded as a promising cancer therapeutic approach. Ginsenoside compound K (CK), an active metabolite of ginsenosides isolated from Panax ginseng C.A. Meyer, has been identif...

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Autores principales: Oh, Jung-Mi, Kim, Eunhee, Chun, Sungkun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747534/
https://www.ncbi.nlm.nih.gov/pubmed/31480534
http://dx.doi.org/10.3390/ijms20174279
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author Oh, Jung-Mi
Kim, Eunhee
Chun, Sungkun
author_facet Oh, Jung-Mi
Kim, Eunhee
Chun, Sungkun
author_sort Oh, Jung-Mi
collection PubMed
description Autophagy can result in cellular adaptation, as well as cell survival or cell death. Modulation of autophagy is increasingly regarded as a promising cancer therapeutic approach. Ginsenoside compound K (CK), an active metabolite of ginsenosides isolated from Panax ginseng C.A. Meyer, has been identified to inhibit growth of cancer cell lines. However, the molecular mechanisms of CK effects on autophagy and neuroblastoma cell death have not yet been investigated. In the present study, CK inhibited neuroblastoma cell proliferation in vitro and in vivo. Treatment by CK also induced the accumulation of sub-G1 population, and caspase-dependent apoptosis in neuroblastoma cells. In addition, CK promotes autophagosome accumulation by inducing early-stage autophagy but inhibits autophagic flux by blocking of autophagosome and lysosome fusion, the step of late-stage autophagy. This effect of CK appears to be mediated through the induction of intracellular reactive oxygen species (ROS) and mitochondria membrane potential loss. Moreover, chloroquine, an autophagy flux inhibitor, further promoted CK-induced apoptosis, mitochondrial ROS induction, and mitochondria damage. Interestingly, those promoted phenomena were rescued by co-treatment with a ROS scavenging agent and an autophagy inducer. Taken together, our findings suggest that ginsenoside CK induced ROS-mediated apoptosis and autophagic flux inhibition, and the combination of CK with chloroquine, a pharmacological inhibitor of autophagy, may be a novel therapeutic potential for the treatment of neuroblastoma.
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spelling pubmed-67475342019-09-27 Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo Oh, Jung-Mi Kim, Eunhee Chun, Sungkun Int J Mol Sci Article Autophagy can result in cellular adaptation, as well as cell survival or cell death. Modulation of autophagy is increasingly regarded as a promising cancer therapeutic approach. Ginsenoside compound K (CK), an active metabolite of ginsenosides isolated from Panax ginseng C.A. Meyer, has been identified to inhibit growth of cancer cell lines. However, the molecular mechanisms of CK effects on autophagy and neuroblastoma cell death have not yet been investigated. In the present study, CK inhibited neuroblastoma cell proliferation in vitro and in vivo. Treatment by CK also induced the accumulation of sub-G1 population, and caspase-dependent apoptosis in neuroblastoma cells. In addition, CK promotes autophagosome accumulation by inducing early-stage autophagy but inhibits autophagic flux by blocking of autophagosome and lysosome fusion, the step of late-stage autophagy. This effect of CK appears to be mediated through the induction of intracellular reactive oxygen species (ROS) and mitochondria membrane potential loss. Moreover, chloroquine, an autophagy flux inhibitor, further promoted CK-induced apoptosis, mitochondrial ROS induction, and mitochondria damage. Interestingly, those promoted phenomena were rescued by co-treatment with a ROS scavenging agent and an autophagy inducer. Taken together, our findings suggest that ginsenoside CK induced ROS-mediated apoptosis and autophagic flux inhibition, and the combination of CK with chloroquine, a pharmacological inhibitor of autophagy, may be a novel therapeutic potential for the treatment of neuroblastoma. MDPI 2019-09-01 /pmc/articles/PMC6747534/ /pubmed/31480534 http://dx.doi.org/10.3390/ijms20174279 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Jung-Mi
Kim, Eunhee
Chun, Sungkun
Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
title Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
title_full Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
title_fullStr Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
title_full_unstemmed Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
title_short Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
title_sort ginsenoside compound k induces ros-mediated apoptosis and autophagic inhibition in human neuroblastoma cells in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747534/
https://www.ncbi.nlm.nih.gov/pubmed/31480534
http://dx.doi.org/10.3390/ijms20174279
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