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

Dong Gun Kim, Kyung Hee Jung, Da Gyum Lee, Jung Ho Yoon, Kyeong Sook Choi, Sung Won Kwon, Han Ming Shen, Michael J. Morgan, Soon Sun Hong, You Sun Kim

Research output: Contribution to journalArticle

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4438-4451
Number of pages14
JournalOncotarget
Volume5
Issue number12
DOIs
StatePublished - 2014

Keywords

  • Autophagy
  • Cell death
  • Doxorubicin
  • HCC

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of '20(S)-Ginsenoside Rg<sub>3</sub> is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin'. Together they form a unique fingerprint.

  • Cite this

    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. https://doi.org/10.18632/oncotarget.2034