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

Lee,Yun-Sun; Lee,Da-Gyum; Lee,Ju-Yeon; Kim,Tae  Ryong; Hong,Soon-Sun; Kwon,Sung  Won; Kim,You-Sun

doi:10.3892/ijo.2013.1964

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

Authors:
- Yun-Sun Lee
- Da-Gyum Lee
- Ju-Yeon Lee
- Tae Ryong Kim
- Soon-Sun Hong
- Sung Won Kwon
- You-Sun Kim
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Affiliations: Institute for Medical Sciences, Ajou University School of Medicine, Suwon 443-749, Republic of Korea, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea, Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea
Published online on: May 27, 2013 https://doi.org/10.3892/ijo.2013.1964
Pages: 591-599

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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.

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