ginsenoside-rg3 and benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone

Ginsenoside is known to have potential cancer-preventive activities. The major active components in red ginseng consist of a variety of ginsenosides including Rg3, Rg5 and Rk1, each of which has different pharmacological activities. Among these, Rg3 has been reported to exert anticancer activities through inhibition of angiogenesis and cell proliferation. However, the effects of Rg3 and its molecular mechanism on glioblastoma multiforme (GBM) remain unclear. Therefore, it is essential to develop a greater understanding of this novel compound. In the present study, we investigated the effects of Rg3 on a human glioblastoma cell line and its molecular signaling mechanism. The mechanisms of apoptosis by ginsenoside Rg3 were related with the MEK signaling pathway and reactive oxygen species. Our data suggest that ginsenoside Rg3 is a novel agent for the chemotherapy of GBM.

Topics: Amino Acid Chloromethyl Ketones; Antioxidants; Apoptosis; Blotting, Western; Brain Neoplasms; Caspases; Cell Proliferation; Flow Cytometry; Ginsenosides; Glioblastoma; Humans; Immunoenzyme Techniques; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinases; Panax; Reactive Oxygen Species; Signal Transduction; Tumor Cells, Cultured

Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and significantly increased the levels of the pro-apoptotic regulator, Bax, while decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53 significantly blocked Rh2-induced cell death as well as vacuole formation, suggesting that both types of cell death induced by Rh2 are mediated by p53 activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF-κB survival pathway. Blockage of ROS by NAC or catalase inhibited the activation of NF-κB signaling and enhanced Rh2-induced cell death, suggesting that the anti-cancer effect of Rh2 can be enhanced by antioxidants.

Topics: Acetylcysteine; Amino Acid Chloromethyl Ketones; Apoptosis; Apoptosis Regulatory Proteins; Blotting, Western; Caspase Inhibitors; Caspases; Cell Death; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Free Radical Scavengers; Ginsenosides; HCT116 Cells; HEK293 Cells; Humans; Mutation; NF-kappa B; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53; Vacuoles