ginsenoside-rg3 and Glioblastoma

Glioblastoma (GBM) is the most common primary malignant intracranial tumor. Due to its high morbidity, high mortality, high recurrence rate, and low cure rate, it has brought great difficulty for treatment. Although the current treatment is multimodal, including surgical resection, radiotherapy, and chemotherapy, it does not significantly improve survival time. The dismal prognosis and inevitable recurrence as well as resistance to chemoradiotherapy may be related to its highly cellular heterogeneity and multiple subclonal populations. Traditional Chinese medicine has its own unique advantages in the prevention and treatment of it. A comprehensive literature search of anti-glioblastoma active ingredients and derivatives from traditional Chinese medicine was carried out in literature published in PubMed, Scopus, Web of Science Cochrane library, CNKI, Wanfang, and VIP database. Hence, this article systematically reviews experimental research progress of some traditional Chinese medicine in treatment of glioblastoma from two aspects: strengthening vital qi and eliminating pathogenic qi. Among, strengthening vital qi medicine includes panax ginseng, licorice, lycium barbarum, angelica sinensis; eliminating pathogenic medicine includes salvia miltiorrhiza bunge, scutellaria baicalensis, coptis rhizoma, thunder god vine, and sophora flavescens. We found that the same active ingredient can act on different signaling pathways, such as ginsenoside Rg3 inhibited proliferation and induced apoptosis via the AKT, MEK signal pathway. Hence, this multi-target, multi-level pathway may bring on a new dawn for the treatment of glioblastoma.

Topics: Animals; Antineoplastic Agents; Drugs, Chinese Herbal; Ginsenosides; Glioblastoma; Humans; Medicine, Chinese Traditional

Topics: Animals; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Brain Neoplasms; Cell Line, Tumor; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Ginsenosides; Glioblastoma; Humans; Male; Mice, Nude; O(6)-Methylguanine-DNA Methyltransferase; Temozolomide; Wnt Signaling Pathway; Xenograft Model Antitumor Assays

Glioblastoma is the most common and deadly primary brain tumor in adults. Low-dose,metronomic (LDM) temozolomide (TMZ) displays improved efficacy in the treatment of glioblastoma by targeting angiogenesis, but has a limited effect on recurrence. The antiangiogenesis drug ginsenoside Rg3 (RG3) is the main active ingredient of ginseng, a popular herbal medicine.. Using an in vitro and a rat model of an orthotopic glioma allograft, this study was to determine whether RG3 enhanced the antiangiogenesis activity of LDM TMZ in the treatment of glioblastoma.. Our results showed that combined use of TMZ with RG3 displayed additive inhibition on proliferation of both human umbilical vein endothelial cells (HUVEC) and rat C6 glioma cells in vitro. They additively arrested cell cycle, increased apoptosis, and decreased VEGF-A and BCL-2 expression in HUVEC. Antiangiogenesis effect was also evaluated in the rat model of orthotopic glioma allograft, based upon markers including relative cerebral blood volume (rCBV) by magnetic resonance imaging (MRI), VEGF levels and microvessel density (MVD)/CD34 staining. LDM TMZ alone was potent in suppressing angiogenesis and tumor growth, whereas RG3 alone only had modest antiangiogenesis effects. Combined treatment significantly and additively suppressed angiogenesis, without additive inhibitory effects on allografted tumor growth.. These data provide evidence showing the efficacy of LDM TMZ on glioma treatment. The combined additive antiangiogenesis effect suggests that RG3 has the potential to further increase the efficacy of LDM TMZ in the treatment of glioblastoma.

Topics: Administration, Metronomic; Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Dacarbazine; Drug Synergism; Gene Expression Regulation, Neoplastic; Ginsenosides; Glioblastoma; Human Umbilical Vein Endothelial Cells; Humans; Rats; Temozolomide; Xenograft Model Antitumor Assays

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