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.

Marine actinomycete crude extracts with potent TRAIL-resistance overcoming activity against breast cancer cells

“…They are a group of bacteria, reported to produce great variety of bioactive secondary metabolites and represent a focal point in the search for novel antimicrobials and anticancer agents (36,37). The cytotoxic effect of several plant and marine sponge extracts against various tumor cell lines was reported (38)(39)(40)(41)(42)(43). However, the anticancer effect of crude extracts isolated from marine microorganisms has not been studied yet.…”

Ginseng for Liver Injury: Friend or Foe?

“…RG exhibits an anticarcinogenic effect on the development of DEN-induced liver cancer in rats [83]. RG promotes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-derived apoptosis in HepG2, Huh-7, and Hep3B cell lines via up-regulation of C/EBP homologous protein [84]. In extensive preclinical and epidemiological studies, RG has been shown to have cancer-preventive effects on many types of cancers, not just liver cancer [85,86].…”

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death

“…Mechanisms have been suggested for the anticancer functions of RGE; RGE reportedly leads to decreased vascular endothelial growth factor expression and inhibitory effects on nuclear factor-κB activity [4], [5], [6], [7], [8], [9]. Our previous study suggested that RGE promotes tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL)-induced cell death in hepatocellular carcinoma (HCC) cells by inducing upregulation of death receptor 5 expression downstream of increased expression of CCAAT-enhancer-binding protein homologous protein (CHOP) [10], [11], indicating that RGE could potentially be further utilized as a chemosensitizer for anticancer drugs.…”