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 language | English (US) |
|---|---|
| Journal | Journal of Ginseng Research |
| DOIs | |
| State | Accepted/In press - 2017 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85028949580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028949580&partnerID=8YFLogxK
U2 - 10.1016/j.jgr.2017.08.006
DO - 10.1016/j.jgr.2017.08.006
M3 - Article
C2 - 30662297
AN - SCOPUS:85028949580
JO - Journal of Ginseng Research
JF - Journal of Ginseng Research
SN - 1226-8453
ER -