Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.2034
Title: 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin
Authors: Kim, D.-G
Jung, K.H
Lee, D.-G
Yoon, J.-H
Choi, K.S
Kwon, S.W
Shen, H.-M 
Morgan, M.J
Hong, S.-S
Kim, Y.-S
Keywords: autophagy protein 5
bafilomycin A1
caspase 3
chloroquine
cycloheximide
death receptor 5
doxorubicin
ginsenoside Rg 3
growth arrest and DNA damage inducible protein 153
LC3 II protein
membrane protein
protein p62
unclassified drug
antineoplastic antibiotic
doxorubicin
ginsenoside
ginsenoside Rg 3
adjuvant therapy
animal cell
animal experiment
animal model
animal tissue
article
autophagosome
autophagy
cancer combination chemotherapy
cancer inhibition
cell death
chemosensitization
controlled study
dose time effect relation
drug effect
drug efficacy
drug inhibition
drug mechanism
drug potentiation
drug response
drug tolerability
enantiomer
enzyme activation
gene expression
ginseng
in vitro study
in vivo study
liver cell carcinoma
male
mouse
nonhuman
protein cleavage
protein stability
tumor volume
tumor xenograft
upregulation
autophagy
Carcinoma, Hepatocellular
female
human
Liver Neoplasms
Antibiotics, Antineoplastic
Autophagy
Carcinoma, Hepatocellular
Doxorubicin
Female
Ginsenosides
Humans
Liver Neoplasms
Male
Issue Date: 2014
Citation: Kim, D.-G, Jung, K.H, Lee, D.-G, Yoon, J.-H, Choi, K.S, Kwon, S.W, Shen, H.-M, Morgan, M.J, Hong, S.-S, Kim, Y.-S (2014). 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. Oncotarget 5 (12) : 4438-4451. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.2034
Rights: Attribution 4.0 International
Abstract: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. High mortality from HCC is mainly due to widespread prevalence and the lack of effective treatment, since systemic chemotherapy is ineffective, while the targeted agent Sorafenib extends median survival only briefly. The steroidal saponin 20(S)-ginsenoside Rg3 from Panax ginseng C.A. Meyer is proposed to chemosensitize to various therapeutic drugs through an unknown mechanism. Since autophagy often serves as cell survival mechanism in cancer cells exposed to chemotherapeutic agents, we examined the ability of Rg3 to inhibit autophagy and chemosensitize HCC cell lines to doxorubicin in vitro. We show that Rg3 inhibits late stage autophagy, possibly through changes in gene expression. Doxorubicin-induced autophagy plays a protective role in HCC cells, and therefore Rg3 treatment synergizes with doxorubicin to kill HCC cell lines, but the combination is relatively nontoxic in normal liver cells. In addition, Rg3 was well-tolerated in mice and synergized with doxorubicin to inhibit tumor growth in HCC xenografts in vivo. Since novel in vivo inhibitors of autophagy are desirable for clinical use, we propose that Rg3 is such a compound, and that combination therapy with classical chemotherapeutic drugs may represent an effective therapeutic strategy for HCC treatment.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/181780
ISSN: 19492553
DOI: 10.18632/oncotarget.2034
Rights: Attribution 4.0 International
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