ginsenoside-rg3 and Glioma

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

A total of 54 natural origin compounds were evaluated for their activity in inhibiting the proliferation of glioma cells. Results showed that four Aesculus polyhydroxylated triterpenoid saponins (3-6), six Gleditsia triterpenoid saponins (7-12), and five phenolic compounds (43-46, 51) had dose-dependent activity suppressing the proliferation of both C6 and U251 cells. Structure-activity relationship analysis suggested that the acetyl group at C-28 for the Aesculus saponins and the monoterpenic acid moiety for the Gleditsia saponins could be critical for the activity of these active compounds. Aesculioside H (4), gleditsioside A (7), and feuric acid 3,4-dihydroxyphenethyl ester (FADPE, 46) were the three most active compounds from the different types of the active compounds and induced apoptosis and necrosis in glioma cells.

Topics: Animals; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glioma; Humans; Phenols; Plant Extracts; Rats; Saponins; Structure-Activity Relationship; Triterpenes

Therapy-induced senescence, an irreversible growth arrest, in cancer cells is regarded as a novel functional target that may improve cancer therapy. 20(S)-ginsenoside Rg3 [20(S)-Rg3], a chemical component extracted from Panax ginseng, has recently emerged as an effective anticancer medicine with evident antitumor effects and no observed toxic adverse reactions. We report here that chronic treatment with 20(S)-Rg3 in a sub-lethal concentration induced senescence-like growth arrest in human glioma cells. Glioma cells treated with 20(S)-Rg3 showed high expression of senescence-associated β-galactosidase, followed by upregulation of the CDK inhibitors p21 and p16. Moreover, reactive oxygen species (ROS) generation markedly increased in 20(S)-Rg3-treated cells compared with control cells. Consistently, co-incubation with the antioxidant N-acetyl cysteine interfered with 20(S)-Rg3-induced senescence in glioma cells. In addition, 20(S)-Rg3-induced-activation of Akt was associated with increased ROS levels, and depletion of Akt partially prevented 20(S)-Rg3-induced ROS generation and senescence induction in glioma cells. Furthermore, 20(S)-Rg3-induced senescence was partially rescued when the p53/p21 pathway was inactivated. Our data indicate that 20(S)-Rg3 induces senescence-like growth arrest in human glioma cancer through the Akt and p53/p21-dependent signaling pathways. This is the first report of a pro-senescent effect of 20(S)-Rg3 in cancer cells.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p21; Enzyme Activation; Ginsenosides; Glioma; Humans; Mitochondria; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53