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Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells
Tang Z.-H.1; Li T.1; Chang L.-L.2; Zhu H.2; Tong Y.-G.3,4; Chen X.-P.1; Wang Y.-T.1; Lu J.-J.1
2014
Source PublicationJournal of Agricultural and Food Chemistry
ISSN218561
Volume62Issue:49Pages:11910
Abstract

Glycyrrhetinic acid (GA), one of the main constituents of the famous Chinese medicinal herb and food additive licorice (Glycyrrhiza uralensis Fisch), has been indicated to possess potential anticancer effects and is widely utilized in hepatocellular carcinoma (HCC) targeted drug delivery systems (TDDS) due to the highly expressed target binding sites of GA on HCC cells. This study found that GA reduced the cell viability, increased the release of lactate dehydrogenase, and enhanced the expression of Bax, cleaved caspase-3, and LC3-II in HCC cells. The GA-triggered autophagy has been further confirmed by monodansylcadaverine staining as well as transmission electron microscopy analysis. The cell viability was obviously decreased whereas the expression of cleaved caspases was significantly increased when inhibition of autophagy by choloroquine or bafilomycin A1, suggesting that GA triggered a protective autophagy. Extracellular regulated protein kinase (ERK) was activated after treatment with GA in HepG2 cells and pretreatment with U0126 or PD98059, the MEK inhibitors, reversed GA-triggered autophagy as evidenced by decreased expression of LC3-II and formation of autophagosomes, respectively. Furthermore, GA-induced cell death and apoptosis were enhanced after pretreatment with PD98059. This is the first report that GA triggers a protective autophagy in HCC cells via activation of ERK, which might attenuate the anticancer effects of GA or chemotherapeutic drugs loaded with GA-modified TDDS. © 2014 American Chemical Society.

KeywordAutophagy Erk Glycyrrhetinic Acid Hepatocellular Carcinoma Protective
DOI10.1021/jf503968k
URLView the original
Indexed BySCI
Language英语
WOS Research AreaAgriculture ; Chemistry ; Food Science & Technology
WOS SubjectAgriculture, Multidisciplinary ; Chemistry, Applied ; Food Science & Technology
WOS IDWOS:000346321400015
The Source to ArticleScopus
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Cited Times [WOS]:31   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Zhejiang Province Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China
3.Department of Pathology, Xinxiang Medical University, 601 East Jinsui Ave., Xinxiang, Henan, China
4.Department of Medicine, Cedars−Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, California 90048, United States
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Tang Z.-H.,Li T.,Chang L.-L.,et al. Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells[J]. Journal of Agricultural and Food Chemistry,2014,62(49):11910.
APA Tang Z.-H..,Li T..,Chang L.-L..,Zhu H..,Tong Y.-G..,...&Lu J.-J..(2014).Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells.Journal of Agricultural and Food Chemistry,62(49),11910.
MLA Tang Z.-H.,et al."Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells".Journal of Agricultural and Food Chemistry 62.49(2014):11910.
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