benzofurans has been researched along with Brain-Neoplasms* in 16 studies
1 review(s) available for benzofurans and Brain-Neoplasms
1 trial(s) available for benzofurans and Brain-Neoplasms
15 other study(ies) available for benzofurans and Brain-Neoplasms
| Article | Year |
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Fraxinellone inhibits progression of glioblastoma via regulating the SIRT3 signaling pathway.
Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo. Topics: Adult; Animals; Apoptosis; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Reactive Oxygen Species; Signal Transduction; Sirtuin 3 | 2022 |
Combination LSD1 and HOTAIR-EZH2 inhibition disrupts cell cycle processes and induces apoptosis in glioblastoma cells.
Glioblastoma (GBM) is the most common primary central nervous system tumor and has a poor prognosis, with a median survival time of only 14 months from diagnosis. Abnormally expressed long noncoding RNAs (lncRNAs) are important epigenetic regulators of chromatin modification and gene expression regulation in tumors, including GBM. We previously showed that the lncRNA HOTAIR is related to the cell cycle progression and can be used as an independent predictor in GBM. Lysine-specific demethylase 1 (LSD1), binding to 3' domain of HOTAIR, specifically removes mono- and di-methyl marks from H3 lysine 4 (H3K4) and plays key roles during carcinogenesis. In this study, we combined a HOTAIR-EZH2 disrupting agent and an LSD1 inhibitor, AC1Q3QWB (AQB) and GSK-LSD1, respectively, to block the two functional domains of HOTAIR and potentially provide therapeutic benefit in the treatment of GBM. Using an Agilent Human ceRNA Microarray, we identified tumor suppressor genes upregulated by AQB and GSK-LSD1, followed by Chromatin immunoprecipitation (ChIP) assays to explore the epigenetic mechanisms of genes activation. Microarray analysis showed that AQB and GSK-LSD1 regulate cell cycle processes and induces apoptosis in GBM cell lines. Furthermore, we found that the combination of AQB and GSK-LSD1 showed a powerful effect of inhibiting cell cycle processes by targeting CDKN1A, whereas apoptosis promoting effects of combination therapy were mediated by BBC3 in vitro. ChIP assays revealed that GSK-LSD1 and AQB regulate P21 and PUMA, respectively via upregulating H3K4me2 and downregulating H3K27me3. Combination therapy with AQB and GSK-LSD1 on tumor malignancy in vitro and GBM patient-derived xenograft (PDX) models shows enhanced anti-tumor efficacy and appears to be a promising new strategy for GBM treatment through its effects on epigenetic regulation. Topics: Animals; Apoptosis; Benzofurans; Brain Neoplasms; Cell Cycle; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; Enhancer of Zeste Homolog 2 Protein; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Glioblastoma; Histone Demethylases; Humans; Mice, Inbred BALB C; Mice, Nude; RNA, Long Noncoding | 2021 |
Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using (
Glioblastoma multiforme (GBM) is the most devastating primary brain tumour characterised by infiltrative growth and resistance to therapies. According to recent research, the sigma-1 receptor (sig1R), an endoplasmic reticulum chaperone protein, is involved in signaling pathways assumed to control the proliferation of cancer cells and thus could serve as candidate for molecular characterisation of GBM. To test this hypothesis, we used the clinically applied sig1R-ligand ( Topics: Animals; Autoradiography; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; Female; Fluorine Radioisotopes; Glioblastoma; Humans; Magnetic Resonance Imaging; Mice; Mice, Knockout; Mice, Nude; Molecular Imaging; Piperidines; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, sigma; Sigma-1 Receptor; Transplantation, Heterologous | 2020 |
Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes.
Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM. Even though chemotherapy extends the survival of patients, there are many undesirable side effects, and most cases show resistance to TMZ. FL3 is a synthetic flavagline which displays potent anticancer activities, and is known to inhibit cell proliferation, by provoking cell cycle arrest, and leads to apoptosis in a lot of cancer cell lines. However, the effect of FL3 in glioblastoma cancer cells has not yet been examined. Hypoxia is a major problem for patients with GBM, resulting in tumor resistance and aggressiveness. In this study, we explore the effect of FL3 in glioblastoma cells under normoxia and hypoxia conditions. Our results clearly indicate that this synthetic flavagline inhibits cell proliferation and induced senescence in glioblastoma cells cultured under both conditions. In addition, FL3 treatment had no effect on human brain astrocytes. These findings support the notion that the FL3 molecule could be used in combination with other chemotherapeutic agents or other therapies in glioblastoma treatments. Topics: Aglaia; Anaerobiosis; Antineoplastic Agents; Apoptosis; Astrocytes; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cellular Senescence; G2 Phase Cell Cycle Checkpoints; Glioblastoma; Humans; Plant Preparations | 2020 |
Proapoptotic effects of novel thiazole derivative on human glioma cells.
The aim of the present study was to investigate the antiproliferative and proapoptotic actions of N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide derivative (compound 5) in glioma cells in comparison with the actions of temozolomide (TMZ) and doxorubicin (Dox), used as positive controls. The antiproliferative activity of the compound 5, TMZ, and Dox on human glioblastoma U251 and human glioblastoma multiform T98G cells was measured using the MTT test. Western blot analysis, fluorescent microscopy, agarose gel retardation assay, flow cytometric analysis, and the DNA comet assay under alkaline conditions were carried out to study the effect of compound 5 on U251 cells. This compound showed ~20 times higher cytotoxicity toward U251 and T98G cells compared with the effects of TMZ and approximately two times higher activity than that of the Dox. Compound 5 induced apoptosis in U251 cells by PARP1 and caspase 3 cleavage mechanisms, also inducing an increase in the level of Bax and Bim proapoptotic proteins and a decrease in the level of phosho-ERK1/2 kinase. The cytotoxicity of compound 5 was associated with an increase in the production of the hydrogen peroxide and the formation of DNA single-strand breaks. This compound 5 did not intercalate into a DNA molecule. Thus, the novel thiazole derivative (compound 5) proved to be a potential antiglioma drug that showed much higher cytotoxic action on human glioma cells compared with the effects of TMZ and Dox. Its cytotoxicity is associated with apoptosis induction, production of the reactive oxygen species, and formation of DNA single-strand breaks without significant DNA intercalation. Topics: Antineoplastic Agents; Apoptosis; Benzofurans; Brain Neoplasms; Cell Line, Tumor; DNA Damage; Doxorubicin; Glioblastoma; Humans; Inhibitory Concentration 50; Intercalating Agents; Reactive Oxygen Species; Temozolomide; Thiazoles | 2019 |
Salvianolic acid B renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction.
Glioma remains the leading cause of brain tumor-related death worldwide, and radiation is a standard adjuvant therapy with proven efficacy. Salvianolic acid B (SalB), a bioactive compound isolated from Radix Salviae, has been shown to exert anti-cancer effects in many cancer cell lines, including glioma. This study aimed to investigate whether SalB could affect response to radiation in human glioma cells. We found that SalB decreased cell viability of U87 cells in a-dose-dependent manner. A subthreshold dose of SalB at 0.5 μM, which had no effect on cell viability and apoptosis, significantly increased radiation sensitivity of U87 cells in a dose- and time-dependent manner, but had no effect on sensitivity to temozolomide (TMZ). Similar results were also observed in human glioma U373 cells. In addition, SalB aggravated the radiation-induced apoptosis and mitochondrial dysfunction, as measured by mitochondrial Ca Topics: Apoptosis; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Drugs, Chinese Herbal; Gene Knockdown Techniques; Glioma; Humans; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Neurons; Radiation-Sensitizing Agents; Radiation, Ionizing; RNA, Small Interfering | 2018 |
Expression of the zinc importer protein ZIP9/SLC39A9 in glioblastoma cells affects phosphorylation states of p53 and GSK-3β and causes increased cell migration.
Zinc importer proteins (ZIPs) have been proven as important molecular regulators in different cancers. As a member of the solute carrier family, ZIP9/SLC39A9 is overexpressed in prostate and breast cancer and affects B-cell receptor signaling. Here, we present data indicating that changes in intracellular zinc levels in glioblastoma cells can cause enhanced cell survival and cell migration, both hallmarks of the disease process. In particular, treatment of human glioblastoma cells with sublethal doses of cell-permeable heavy metal (Zn Topics: Benzofurans; Brain Neoplasms; Cation Transport Proteins; Cell Line, Tumor; Cell Movement; Chelating Agents; Enzyme Inhibitors; Ethylenediamines; Gene Expression Regulation, Neoplastic; Glioblastoma; Glycogen Synthase Kinase 3 beta; Humans; Oxadiazoles; Phosphorylation; Transfection; Tumor Suppressor Protein p53 | 2016 |
Salvianolic acid B induces apoptosis in human glioma U87 cells through p38-mediated ROS generation.
Salvianolic acid B (SalB), the main water-soluble bioactive compounds isolated from the traditional Chinese medical herb Danshen, has been shown to exert anti-cancer effect in several cancer cell lines. The aim of our study was to investigate the potential anti-cancer effect of SalB in human glioma U87 cells. We found that treatment with SalB significantly decreased cell viability of U87 cells in a dose- and time-dependent manner. SalB also enhanced the intracellular ROS generation and induced apoptotic cell death in U87 cells. Western blot analysis suggested that SalB increased the phosphorylation of p38 MAPK and p53 in a dose-dependent manner. Moreover, blocking p38 activation by specific inhibitor SB203580 or p38 specific siRNA partly reversed the anti-proliferative and pro-apoptotic effects, and ROS production induced by SalB treatment. The anti-tumor activity of SalB in vivo was also demonstrated in U87 xenograft glioma model. All of these findings extended the anti-cancer effect of SalB in human glioma cell lines, and suggested that these inhibitory effects of SalB on U87 glioma cell growth might be associated with p38 activation mediated ROS generation. Thus, SalB might be concerned as an effective and safe natural anticancer agent for glioma prevention and treatment. Topics: Animals; Antineoplastic Agents; Apoptosis; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Glioma; Humans; Mice; p38 Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Tumor Suppressor Protein p53 | 2013 |
Lobarstin enhances chemosensitivity in human glioblastoma T98G cells.
Lobarstin is a metabolite occurring from the Antarctic lichen Stereocaulon alpnum. Human glioblastoma is highly resistant to chemotherapy with temozolomide. Lobarstin was examined for its effect on glioblastoma.. Temozolomide-resistant T98G cells were subjected to toxicity test with temozolomide and/or lobarstin. DNA damage and recovery was assessed by the alkaline comet assay and expression of DNA repair genes was examined by RT-PCR and western blot analysis.. Lobarstin alone at 40 μM was toxic against T98G, but had no effect in primary human fibroblasts. Co-treatment of lobarstin with temozolomide yielded enhanced toxicity. Temozolomide-alone or with lobarstin co-treatment gave similar extent of DNA damage. However, the recovery was reduced in co-treated cells. Expression of DNA repair genes, O(6)-methylguanine-DNA methyltransferase, poly(ADP-ribose) polymerase 1 and ligase 3 were reduced in lobarstin-treated cells.. Enhanced sensitivity to temozolomide by lobarstin co-treatment may be attributed to reduced DNA repair. Topics: Antineoplastic Agents; Base Sequence; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Comet Assay; Dacarbazine; DNA Damage; DNA Primers; DNA Repair; Drug Synergism; Glioblastoma; Humans; Hydroxybenzoates; O(6)-Methylguanine-DNA Methyltransferase; Reverse Transcriptase Polymerase Chain Reaction; Temozolomide | 2013 |
Overexpression of the orphan receptor Nur77 and its translocation induced by PCH4 may inhibit malignant glioma cell growth and induce cell apoptosis.
In previous study, n-butylidenephthalide (BP), a natural compound from Angelica sinensis, has anti-glioblastoma multiform (GBM) cell effects. In this study, we modified BP structure to increase anti-GBM cell effects. The anti-GBM cell effects of one derivative of BP, (Z)-N-(2-(dimethylamino)ethyl)-2-(3-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)phenoxy)acetamide (PCH4) were tested in vitro and in vivo.. MTT assay and PI/Annexin V assay were performed to evaluate the anti-GBM effects of PCH4. The Nur77 expression and translocation were assayed by RT-PCR and Western blot. The Nur77 siRNA was used to downregulate the Nur77 expression. The JNK inhibitor (SP600125) was used to block the JNK pathway.. The anti-GBM effect of PCH4 is four times more than BP. The IC(50) of PCH4 on DBTRG-05MG cells was 50 µg/ml. Nur77 expression and translocation from the nucleus to the cytoplasm were important in PCH4-induced apoptosis. Furthermore, the downregulation of PCH4-induced Nur77 expression by Nur77 siRNA reduced PCH4-induced apoptosis. In addition, PCH4-induced apoptosis was associated with the JNK pathway. The JNK inhibitor, SP600125, inhibited Nur77 mRNA expression and reduced PCH4-induced apoptosis.. In conclusion, PCH4, a derivative of BP, induced Nur77-mediated apoptosis via the JNK pathway and this mechanism, which is different from that of BP, may explain the increase in the anti-tumor effects on GBM. Topics: Angelica sinensis; Animals; Apoptosis; Benzofurans; Blotting, Western; Brain Neoplasms; Cell Proliferation; DNA-Binding Proteins; Ethylamines; Flow Cytometry; Glioblastoma; Humans; Luciferases; MAP Kinase Kinase 4; Mice; Mice, Nude; Nuclear Receptor Subfamily 4, Group A, Member 1; Nuclear Receptor Subfamily 4, Group A, Member 2; Phthalic Anhydrides; Protein Transport; Receptors, Steroid; Receptors, Thyroid Hormone; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Tumor Cells, Cultured; Xenograft Model Antitumor Assays | 2011 |
Inhibition of invasion-associated thromboxane synthase sensitizes experimental gliomas to gamma-radiation.
The invasion- and apoptosis-associated thromboxane synthase gene encoding an enzyme of the arachidonic acid pathway has been implicated in glioma progression. Furegrelate, a specific inhibitor of thromboxane synthase, blocks cell motility, induces apoptosis and increases sensitivity to drug induced apoptosis in human glioma cells in vitro. The impact of furegrelate on the sensitivity of human glioma cells to gamma-irradiation was analyzed using colony formation assay in vitro and an orthotopic mouse model in vivo. Pre-treatment of glioma cells with furegrelate increases radiation sensitivity of cultured glioma cells. Treatment of experimental gliomas with suboptimal doses of radiation and furegrelate results in a significant decrease in tumor volumes compared to untreated controls. Thus, the specific thromboxane synthase inhibitor furegrelate increases death response induced by gamma-radiation in glioma cells in vitro and sensitizes experimental gliomas to radiation treatment in vivo. Topics: Animals; Animals, Inbred Strains; Astrocytes; Benzofurans; Brain Neoplasms; Cell Survival; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Enzyme Inhibitors; Gamma Rays; Gene Expression Regulation, Neoplastic; Glioma; Humans; Mice; Neoplasm Invasiveness; Radiation Tolerance; Thromboxane-A Synthase; Thromboxanes; Time Factors; Transfection | 2009 |
l-3-n-Butylphthalide ameliorates beta-amyloid-induced neuronal toxicity in cultured neuronal cells.
l-3-n-Butylphthalide (l-NBP), as an anti-cerebral ischemia agent, has been shown to have therapeutic effects on learning and memory deficits induced by chronic cerebral hypoperfusion and Abeta intracerebroventricular infusion in rats. In the present study, we investigated the neuroprotective effects of l-NBP on beta-amyloid (Abeta)25-35-induced neuronal death/apoptosis and potential mechanisms in rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. Abeta25-35 significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that Abeta25-35-induced neurotoxicity. In addition, tau protein hyperphosphorylation was found to increase after Abeta exposure. All of these phenotypes induced by Abeta25-35 were markedly reversed by l-NBP. Pretreatment with l-NBP prior to Abeta25-35 exposure significantly elevated cell viability, and reduced Abeta25-35-induced nuclear fragmentation and early apoptosis. Furthermore, immunoreactivity for hyperphosphorylation tau protein was significantly decreased by l-NBP treatment. Our results suggest that l-NBP may protect neurons against Abeta-induced neurotoxicity via inhibiting tau protein hyperphosphorylation. Topics: Amyloid beta-Peptides; Animals; Apium; Apoptosis; Benzofurans; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Drug Interactions; Hippocampus; Humans; Neuroblastoma; Neurons; Neuroprotective Agents; Peptide Fragments; Plant Extracts; Rats; Rats, Sprague-Dawley | 2008 |
Densities of I2-imidazoline receptors, imidazoline receptor proteins, and MAO-B sites in human gliomas and pituitary adenomas.
Topics: Acromegaly; Adenoma; Benzofurans; Brain Neoplasms; Female; Frontal Lobe; Glioma; Humans; Imidazoles; Imidazoline Receptors; Isoenzymes; Kinetics; Male; Middle Aged; Monoamine Oxidase; Pituitary Gland; Pituitary Neoplasms; Radioligand Assay; Receptors, Drug; Reference Values; Tritium | 1999 |
Thromboxane synthase regulates the migratory phenotype of human glioma cells.
The capacity of glial tumor cells to migrate and diffusely infiltrate normal brain compromises surgical eradication of the disease. Identification of genes associated with invasion may offer novel strategies for anti-invasive therapies. The gene for TXsyn, an enzyme of the arachidonic acid pathway, has been identified by differential mRNA display as being overexpressed in a glioma cell line selected for migration. In this study TXsyn mRNA expression was found in a large panel of glioma cell lines but not in a strain of human astrocytes. Immunohistochemistry demonstrated TXsyn in the parenchyma of glial tumors and in reactive astrocytes, whereas it could not be detected in quiescent astrocytes and oligodendroglia of normal brain. Glioma cell lines showed a wide range of thromboxane B2 formation, the relative expression of which correlated with migration rates of these cells. Migration was effectively blocked by specific inhibitors of TXsyn, such as furegrelate and dazmegrel. Other TXsyn inhibitors and cyclooxygenase inhibitors were less effective. Treatment with specific inhibitors also resulted in a decrease of intercellular adhesion in glioma cells. These data indicate that TXsyn plays a crucial role in the signal transduction of migration in glial tumors and may offer a novel strategy for anti-invasive therapies. Topics: Arachidonic Acids; Aspirin; Astrocytes; Benzofurans; Brain Neoplasms; Cell Adhesion; Cell Movement; Enzyme Induction; Enzyme Inhibitors; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glioma; GTP-Binding Proteins; Humans; Imidazoles; Indomethacin; Lysine; Models, Biological; Neoplasm Proteins; Neoplastic Stem Cells; Oligodendroglia; Pentanoic Acids; Phenotype; Pyridines; RNA, Messenger; RNA, Neoplasm; Signal Transduction; Thromboxane B2; Thromboxane-A Synthase; Tumor Cells, Cultured | 1999 |
[Dopamine-D2 receptor scintigraphy with 123I-iodobenzofuran in malignant melanoma].
In recent publications dopamine-D2 receptor scintigraphy with benzamides was postulated for specific imaging of melanoma. In a prospective study the value of 123I-iodobenzofuran (IBF), a highly specific and affine dopamine-D2 receptor ligand was evaluated for the detection of melanoma metastases. With IBF-D2 receptor scintigraphy only 2 of 17 melanoma metastases could be detected. The interpretation of the abdomen was impaired by the hepatobiliary and renal excretion of the radionuclide. The ratio striatum/frontal cortex of 2.75 +/- 0.49 3 h p.i. demonstrated a high D2-receptor binding of the ligand. IBF-D2-receptor scintigraphy is not suitable as a method of staging melanoma. Topics: Adult; Aged; Benzofurans; Brain Neoplasms; Corpus Striatum; Female; Frontal Lobe; Humans; Iodine Radioisotopes; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prospective Studies; Radionuclide Imaging; Receptors, Dopamine D2; Sensitivity and Specificity | 1995 |