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20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin.

Authors
Kim, DG; Jung, KH; Lee, DG; Yoon, JH; Choi, KS; Kwon, SW; Shen, HM; Morgan, MJ; Hong, SS; Kim, YS
Citation
Oncotarget, 5(12):4438-4451, 2014
Journal Title
Oncotarget
ISSN
1949-2553
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.
MeSH terms
Antibiotics, Antineoplastic/pharmacologyAutophagyCarcinoma, Hepatocellular/drug therapyDoxorubicin/pharmacologyFemaleGinsenosides/administration & dosageGinsenosides/therapeutic useHumansLiver Neoplasms/drug therapyMale
DOI
10.18632/oncotarget.2034
PMID
24970805
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
이, 다겸최, 경숙김, 유선
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