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A formulated red ginseng extract upregulates CHOP and increases TRAIL-mediated cytotoxicity in human hepatocellular carcinoma cells.

Authors
Lee, YS; Lee, DG; Lee, JY; Kim, TR; Hong, SS; Kwon, SW; Kim, YS
Citation
International journal of oncology, 43(2):591-599, 2013
Journal Title
International journal of oncology
ISSN
1019-64391791-2423
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because its cytotoxicity is selective for tumor cells. Despite promising outcomes in clinical trials using this ligand, sustained clinical responses have been impeded because cancer cells acquire resistance to TRAIL-based therapies. Ginseng, a well-known food product consumed globally, has been reported to reduce fatigue and possess antioxidant and antitumor activities. We explored the sensitizing influence of a formulated red ginseng extract (RGE) on TRAIL-derived cell death in hepatocellular carcinoma (HCC) cell lines and the underlying molecular mechanisms responsible for TRAIL sensitization. We found that the RGE promoted TRAIL-derived apoptosis in HepG2, Huh-7 and Hep3B cell lines. We also found that death receptor 5 expression was induced by the RGE and mediated by C/EBP homologous protein (CHOP). shRNA-induced downregulation of CHOP expression effectively suppressed cell death induced by combined treatment with the RGE and TRAIL in the HepG2 cell line, indicating that RGE-related upregulation of the CHOP protein plays an important role in sensitizing TRAIL-derived apoptosis. In summary, we showed that the RGE sensitized human HCC cell lines to TRAIL-derived cell death and could be utilized as a dietary supplement in combination with cancer treatment.
MeSH terms
Apoptosis/drug effectsCarcinoma, Hepatocellular/*metabolismCell Line, TumorDown-Regulation/drug effectsDrug SynergismGinsenosides/chemistry/*pharmacologyHep G2 CellsHumansLiver Neoplasms/*metabolismPanax/*chemistryPlant Extracts/chemistry/*pharmacologyRNA InterferenceRNA, Small InterferingReceptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis/drug effectsTNF-Related Apoptosis-Inducing Ligand/*pharmacologyTranscription Factor CHOP/*biosynthesis/genetics
DOI
10.3892/ijo.2013.1964
PMID
23708152
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
김, 유선
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