Panax ginseng C. A. MEYER (ginseng) is one of the most common herbal medicines in the Orient used for the treatment of disease. Ginseng saponins (ginsenosides) are the major active components in ginseng and possess anti-inflammatory, anti-cancer, and neuroprotective activity. [1][2][3] Of the ginsenosides, Rk1, Rg3, Rg5, F4 2 , etc. are isolated from heat-processed ginseng, Sun Ginseng (SG), but they are not detected in raw or air-dried ginseng. 4,5) The enhanced antitumor activity of SG is attributed to the generation of ginsenosides due to heat processing. 4,6) The molecular mechanisms underlying the anti-tumor activity of SG-derived ginsenosides have not been comprehensively investigated.High telomerase activity is found in the vast majority of human malignant tissues and many immortal cell lines. The fundamental components of telomerase are telomerase reverse transcriptase (hTERT), telomerase RNA (hTR), and telomerase-associated proteins.7) Of these, hTR and telomerase-associated proteins are expressed ubiquitously in both normal and cancerous tissues, 8) whereas hTERT is expressed at high levels in human tumors and either not at all or at very low levels in normal tissues.7) The rate-limiting component of telomerase is hTERT, and thus, the expression level of hTERT correlates with telomerase activity.Fas-associated death domain (FADD) interacts with the cytosolic tail of the Fas/APO-1 receptor by binding to the COOH-terminal death domain (DD) to expose the NH 2 -terminal death effector domain (DED).9,10) Recruitment of caspases-8 and -10 by DED forms the death-inducing signaling complex (DISC), resulting in the oligomerization of these proteases and their subsequent cleavage and activation.
11)Phosphorylation of FADD at Ser194 is involved in the G2/M phase arrest in Burkitt lymphoma and breast cancer cells. 12,13) Members of the mitogen-activated protein kinase (MAPK) family represent one type of serine/threonine protein kinase, and are key modulators of cell activation, including apoptosis and cell cycle progression. To date, three major MAPKs, extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, have been identified. ERK is generally activated by growth factors and is involved in the regulation of cell proliferation.14,15) Activation of ERK is often associated with cell cycle arrest. 16,17) In this study, the mechanism underlying the anti-tumor activity of the ginsenoside Rk1 was investigated by examining the effects of Rk1 on cell growth, telomerase activity, and apoptosis in human hepatocellular carcinoma HepG2 cells.
MATERIALS AND METHODS
ChemicalsThe ginsenoside Rk1 (Fig. 1) was isolated from SG as previously described 6) and confirmed by NMR and MS spectroscopic analysis. The compound was dissolved in dimethylsulfoxide (DMSO) at a concentration of 20 mM and stored at Ϫ20°C. When required, the compound was diluted with medium to the appropriate concentration.Cell Culture and Treatment The human hepatocellular carcinoma cell line HepG2 was purchased from the American Type Cultu...