A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death

Han Hee Park, Seung Won Choi, Gwang Jin Lee, Young Dae Kim, Hyun Jin Noh, Seung Jae Oh, Iseul Yoo, Yu Jin Ha, Gi Bang Koo, Soon Sun Hong, Sung Won Kwon, You Sun Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

Original languageEnglish (US)
JournalJournal of Ginseng Research
DOIs
StateAccepted/In press - 2017

Fingerprint

Panax
doxorubicin
Cell death
Doxorubicin
autophagy
cell death
Autophagy
Cell Death
hepatoma
Fluxes
Hepatocellular Carcinoma
extracts
Green Fluorescent Proteins
green fluorescent protein
Microtubule-Associated Proteins
Oncology
Chemotherapy
Saponins
L-Lactate Dehydrogenase
Liver

Keywords

  • Autophagic flux
  • Cell death
  • Ginseng extract

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Complementary and alternative medicine

Cite this

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death. / Park, Han Hee; Choi, Seung Won; Lee, Gwang Jin; Kim, Young Dae; Noh, Hyun Jin; Oh, Seung Jae; Yoo, Iseul; Ha, Yu Jin; Koo, Gi Bang; Hong, Soon Sun; Kwon, Sung Won; Kim, You Sun.

In: Journal of Ginseng Research, 2017.

Research output: Contribution to journalArticle

Park, HH, Choi, SW, Lee, GJ, Kim, YD, Noh, HJ, Oh, SJ, Yoo, I, Ha, YJ, Koo, GB, Hong, SS, Kwon, SW & Kim, YS 2017, 'A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death', Journal of Ginseng Research. https://doi.org/10.1016/j.jgr.2017.08.006
Park, Han Hee ; Choi, Seung Won ; Lee, Gwang Jin ; Kim, Young Dae ; Noh, Hyun Jin ; Oh, Seung Jae ; Yoo, Iseul ; Ha, Yu Jin ; Koo, Gi Bang ; Hong, Soon Sun ; Kwon, Sung Won ; Kim, You Sun. / A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death. In: Journal of Ginseng Research. 2017.
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abstract = "Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.",
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T1 - A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death

AU - Park, Han Hee

AU - Choi, Seung Won

AU - Lee, Gwang Jin

AU - Kim, Young Dae

AU - Noh, Hyun Jin

AU - Oh, Seung Jae

AU - Yoo, Iseul

AU - Ha, Yu Jin

AU - Koo, Gi Bang

AU - Hong, Soon Sun

AU - Kwon, Sung Won

AU - Kim, You Sun

PY - 2017

Y1 - 2017

N2 - Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

AB - Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

KW - Autophagic flux

KW - Cell death

KW - Ginseng extract

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U2 - 10.1016/j.jgr.2017.08.006

DO - 10.1016/j.jgr.2017.08.006

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JO - Journal of Ginseng Research

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SN - 1226-8453

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