ginsenoside-rg3 and Brain-Neoplasms

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Ginsenosides; Glioma; Liposomes; Mice; Mice, Inbred BALB C; Paclitaxel; Rats; Tumor Microenvironment

In various malignant tumors, NF-kappa B interacting long noncoding RNA (NKILA) displays antitumor activity by inhibiting the NF-kappa B pathway. However, the role of NKILA in gliomas remains unclear. Surprisingly, this study showed that NKILA is significantly upregulated in gliomas, and the increased levels of NKILA were correlated with a decrease in patient survival time. NKILA increased the expression level of hypoxia-inducible factor-1α, and the activity of the hypoxia pathway in gliomas. Furthermore, we demonstrated that NKILA enhances the Warburg effect and angiogenesis in gliomas both in vitro and in vivo. Therefore, NKILA is a potential therapeutic target in gliomas. In addition, we showed that a 20(S)-Rg3 monomer suppresses NKILA accumulation and reverses its stimulation of the Warburg effect and angiogenesis in gliomas, both in vitro and in vivo. Therefore, this study not only identified NKILA as a potential therapeutic target in gliomas, but also demonstrated a practical approach to treatment.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Chickens; Gene Expression Regulation, Neoplastic; Ginsenosides; Glioma; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Neovascularization, Pathologic; RNA, Long Noncoding; Signal Transduction; Survival Analysis; Tumor Hypoxia; Up-Regulation; Warburg Effect, Oncologic

The purpose of this work was to prepare and characterize Angiopep-2 functionalized ginsenoside-Rg3 loaded nanoparticles (ANG-Rg3-NP) and evaluate the therapeutic effect on C6 glioma cells. Nanoparticles were prepared by the emulsion solvent evaporation method. Angiopep-2 was functionalized to nanoparticles via a maleimide-thiol covalent binding reaction to obtain ANG-Rg3-NP. The prepared nanoparticles were evaluated for size, zeta potential, morphology, stability, encapsulation efficiency, loading capacity, and release properties. The cytotoxicity study and targeting effect of ANG-Rg3-NP were evaluated by MTT assay. The study of cellular uptake in C6 glioma cells was performed by fluorescence microscopy and by using a microplate reader. The prepared ANG-Rg3-NP was observed to be uniformly spherical in shape with a particle size at 147.1 ± 2.7 nm. The encapsulation efficiency and loading capacity reached 80.6 ± 3.0% and 27.2 ± 1.4%, respectively. Additionally, ANG-Rg3-NP exhibited a desirable sustained release behavior. In vitro cytotoxicity study indicated that ANG-Rg3-NP could inhibit the proliferation of C6 glioma cells in a concentration-dependent manner. Also, the functionalization of Angiopep-2 made nanoparticles cross the blood-brain barrier more easily and accelerated the cellular uptake of nanoparticles. The ANG-Rg3-NP was a promising brain drug delivery carrier for the treatment of glioma.

Topics: Animals; Antineoplastic Agents, Phytogenic; Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Ginsenosides; Glioma; Nanoparticles; Particle Size; Peptides; Rats; Rats, Sprague-Dawley

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