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

49 Citations (Scopus)

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
StatePublished - 2014

Fingerprint

Autophagy
Doxorubicin
Hepatocellular Carcinoma
Therapeutics
Cell Line
Neoplasms
Panax
Saponins
ginsenoside Rg3
Heterografts
Pharmaceutical Preparations
Cell Survival
Gene Expression
Drug Therapy
Mortality
Liver
Growth

Keywords

  • Autophagy
  • Cell death
  • Doxorubicin
  • HCC

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

Kim, D. G., Jung, K. H., Lee, D. G., Yoon, J. H., Choi, K. S., Kwon, S. W., ... 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.

20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. / Kim, Dong Gun; Jung, Kyung Hee; Lee, Da Gyum; Yoon, Jung Ho; Choi, Kyeong Sook; Kwon, Sung Won; Shen, Han Ming; Morgan, Michael J.; Hong, Soon Sun; Kim, You Sun.

In: Oncotarget, Vol. 5, No. 12, 2014, p. 4438-4451.

Research output: Contribution to journalArticle

Kim, DG, Jung, KH, Lee, DG, Yoon, JH, Choi, KS, Kwon, SW, Shen, HM, Morgan, MJ, Hong, SS & Kim, YS 2014, '20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin', Oncotarget, vol. 5, no. 12, pp. 4438-4451.
Kim DG, Jung KH, Lee DG, Yoon JH, Choi KS, Kwon SW et al. 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. Oncotarget. 2014;5(12):4438-4451.
Kim, Dong Gun ; Jung, Kyung Hee ; Lee, Da Gyum ; Yoon, Jung Ho ; Choi, Kyeong Sook ; Kwon, Sung Won ; Shen, Han Ming ; Morgan, Michael J. ; Hong, Soon Sun ; Kim, You Sun. / 20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. In: Oncotarget. 2014 ; Vol. 5, No. 12. pp. 4438-4451.
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