title: A formulated red ginseng extract upregulates CHOP and increases TRAIL-mediated cytotoxicity in human hepatocellular carcinoma cells.
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.
authors.affiliation: Institute for Medical Sciences, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.
authors.forename: Yun-Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Da-Gyum
authors.initials: DG
authors.lastname: Lee
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Kim
authors.forename: Soon-Sun
authors.initials: SS
authors.lastname: Hong
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kwon
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: C497249:DDIT3 protein, human; D036145:Ginsenosides; D010936:Plant Extracts; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D051742:Transcription Factor CHOP