Brefeldin A Induces Apoptosis and Cell Cycle Blockade in Glioblastoma Cell Lines

Oncology ◽  
2003 ◽  
Vol 64 (4) ◽  
pp. 459-467 ◽  
Author(s):  
Isabelle Pommepuy ◽  
Faraj Terro ◽  
Barbara Petit ◽  
Frank Trimoreau ◽  
Virginie Bellet ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Brefeldin A ◽  
Glioblastoma Cell ◽  
Glioblastoma Cell Lines

scholarly journals Differential Effects of Selective COX-2 Inhibitors on Cell Cycle Regulation and Proliferation of Glioblastoma Cell Lines

2004 ◽  
Vol 3 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Adel Kardosh ◽  
Martina Blumenthal ◽  
Wei Jun Wang ◽  
Thomas C. Chen ◽  
Axel H. Schonthal
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Regulation ◽  
Glioblastoma Cell ◽  
Differential Effects ◽  
Cox 2 ◽  
Cycle Regulation ◽  
Cox 2 Inhibitors ◽  
Glioblastoma Cell Lines

scholarly journals Moschamine inhibits proliferation of glioblastoma cells via cell cycle arrest and apoptosis

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770574 ◽  
Author(s):  
George A Alexiou ◽  
Diamanto Lazari ◽  
Georgios Markopoulos ◽  
Evrysthenis Vartholomatos ◽  
Entela Hodaj ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Indole Alkaloid ◽  
Glioblastoma Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest ◽  
Cd15 Expression ◽  
Glioblastoma Cell Lines

Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. Moschamine is an indole alkaloid that has a serotoninergic and cyclooxygenase inhibitory effect. In this study, we sought to determine whether moschamine could exert cytotoxic and cytostatic effects on glioma cells in vitro. Moschamine was tested for toxicity in zebrafish. We investigated the effect of moschamine on U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the xCELLigence system. Apoptosis (annexin–propidium iodide), cell cycle, and CD24/CD44/CD56/CD15 expression were tested with flow cytometry. Treatment with moschamine significantly reduced cell viability in both cell lines tested. Induction of cell death and cell cycle arrest was confirmed with flow cytometry in both cell lines. After treatment with moschamine, there was a dose-dependent decrease in CD24 and CD44 expression, whereas there was no change in CD56 and CD15 expression in T98G cell line. The zebrafish mortality on the fifth post-fertilization day was zero even for 1 mM of moschamine concentration. The treatment of glioblastoma cell lines with moschamine may represent a novel strategy for targeting glioblastoma.

scholarly journals In Vitro Activity of Monofunctional Pt-II Complex Based on 8-Aminoquinoline against Human Glioblastoma

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2101
Author(s):  
Valentina Coccè ◽  
Isabella Rimoldi ◽  
Giorgio Facchetti ◽  
Emilio Ciusani ◽  
Giulio Alessandri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Significant Activity ◽  
Glioblastoma Cell ◽  
Main Target ◽  
Human Carcinomas ◽  
A Minor ◽  
Glioblastoma Cell Lines ◽  
Minor Activity

A new cationic Pt(II) complex bearing 8-aminoquinoline as chelating ligand (called Pt-8AQ) was evaluated against two human carcinomas, one mesothelioma, and three glioblastoma cell lines. The in vitro comparison to the clinically approved CisPt showed a minor activity of Pt-8AQ against carcinoma and mesothelioma, whereas a significant activity of Pt-8AQ was observed on the proliferation of the three glioblastoma cell lines (U87-MG IC50 = 3.68 ± 0.69 µM; U373-MG IC50 = 11.53 ± 0.16 µM; U138-MG IC50 = 8.05 ± 0.23 µM) that was higher than that observed with the clinically approved CisPt (U87-MG IC50 = 7.27 + 1.80 µM; U373-MG IC50 = 22.69 ± 0.05 µM; U138-MG IC50 = 32.1 ± 4.44 µM). Cell cycle analysis proved that Pt-8AQ significantly affected the cell cycle pattern by increasing the apoptotic cells represented by the sub G0/G1 region related with a downregulation of p53 and Bcl-2. Moreover, an NMR investigation of Pt-8AQ interaction with 9-EtG, GSH, and Mets7 excluded DNA as the main target, suggesting a novel mechanism of action. Our study demonstrated the high stability of Pt-8AQ after incubation at 37 °C and a significant antineoplastic activity on glioblastomas. These features also make Pt-8AQ a good candidate for developing a new selective advanced cell chemotherapy approach in combination with MSCs.

scholarly journals P11.02 Hypothermia effect on glioblastoma cell viability, proliferation and migration

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii42-iii42
Author(s):  
C Fulbert ◽  
C Gaude ◽  
E Sulpice ◽  
S Chabardès ◽  
D Ratel
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Resection Margin ◽  
Moderate Hypothermia ◽  
Glioblastoma Cell ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

Abstract BACKGROUND Glioblastoma is the most common and aggressive primary brain tumor in adults. In spite of intensive treatment, patients have a poor prognosis with a median survival of 14–16 months. After surgical resection followed by postoperative chemoradiation (combined temozolomide treatment and radiotherapy), tumor recurs in the resection margin for more than 90% of patients. This recurrence results from the activation of residual glioblastoma cells beyond the resection cavity by therapy-induced injuries. To handle this issue, we propose therapeutic hypothermia as an adjuvant treatment, in order to place the resection margin in a state of hibernation. In fact, hypothermia was introduced as a promising therapeutic approach in various medical applications like cardiac arrest and pharmaco-resistant epilepsy. Only a few in vitro studies explored the effects of hypothermia on cancer cells and showed promising results. The aim of our work is to investigate the effects of hypothermia on glioblastoma cell proliferation and migration, two key cellular processes involved in cancer progression. MATERIAL AND METHODS We performed in vitro experiments on glioblastoma cell lines with different p53 status and various growth rates. For exploring the therapeutic potential of both mild and moderate hypothermia, we studied their impact on cell viability, proliferation and migration. We also performed cell cycle analysis by quantitation of DNA content using flow cytometry. RESULTS Results were similar for all glioblastoma cell lines, and demonstrated that cells were extremely sensitive to hypothermia. We showed that both mild and moderate hypothermia induced significant changes on glioblastoma cell lines behavior with a strong inhibition of cell proliferation and migration. Moderate hypothermia also affected glioblastoma cell viability and modified their distribution into the cell cycle phases. CONCLUSION Our results were comparable in all glioblastoma cell lines tested, demonstrating a consistent and universal effect of hypothermia. We showed that hypothermia significantly inhibits cell proliferation and migration, which are key processes involved in tumor growth. Proliferation arrest could be explained by the accumulation of cells in the G2/M phase of the cell cycle. Together, these results support hypothermia as a promising adjuvant therapy for glioblastoma patients. Indeed, combined with current treatments, moderate hypothermia applied at the resection margin could prevent tumor recurrence after surgical resection. There is a crucial need to propose innovative glioblastoma treatments, and hypothermia appears as a promising therapeutic way. SUPPORT This work received financial support through grants from the Groupement des Entreprises Françaises de Lutte contre le Cancer (GEFLUC Grenoble - Dauphiné - Savoie) and the Fonds de dotation Clinatec.

scholarly journals Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines

2015 ◽  
Vol 122 (3) ◽  
pp. 547-556 ◽  
Author(s):  
Kevin A. Harvey ◽  
Zhidong Xu ◽  
M. Reza Saaddatzadeh ◽  
Haiyan Wang ◽  
Karen Pollok ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gas Chromatography ◽  
Endothelial Cells ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Flow Cytometric Analysis ◽  
Glioblastoma Cell ◽  
Flow Cytometric ◽  
Growth Inhibitory ◽  
Glioblastoma Cell Lines

OBJECT Glioblastoma is a rapidly infiltrating tumor that consistently rematerializes despite various forms of aggressive treatment. Brain tumors are commonly treated with alkylating drugs, such as lomustine, which are chemotherapeutic agents. Use of these drugs, however, is associated with serious side effects. To reduce the side effects, one approach is to combine lower doses of chemotherapeutic drugs with other nontoxic anticancer agents. In this study, using glioblastoma cell lines, the authors investigated the anticancer effects of lomustine, alone and in combination with docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid normally abundant in the brain and known for its anticancer potential. METHODS Cells were cultured from 3 human-derived tumor cell lines (U87-MG, DB029, and MHBT161) and supplemented with either DHA or lomustine to determine the growth inhibitory potential using WST-1, a mitochondrial functional indicator. Human-derived cerebral cortex microvascular endothelial cells served as a normal phenotypic control. Cellular incorporation of DHA was analyzed by gas chromatography. Using flow cytometric analysis, the DHA and/or lomustine effect on induction of apoptosis and/or necrosis was quantified; subsequently, the DHA and lomustine effect on cell cycle progression was also assessed. Western blot analysis confirmed the role of downstream cellular targets. RESULTS U87-MG growth was inhibited with the supplementation of either DHA (ED50 68.3 μM) or lomustine (ED50 68.1 μM); however, growth inhibition was enhanced when U87-MG cells were administered equimolar doses of each compound, resulting in nearly total growth inhibition at 50 μM. Gas chromatography analysis of the fatty acid profile in DHA-supplemented U87-MG cells resulted in a linear dose-dependent increase in DHA incorporation (< 60 μM). The combination of DHA and lomustine potently induced U87-MG apoptosis and necrosis as indicated by flow cytometric analysis. Activation of caspase-3 and poly (ADP-ribose) polymerase (PARP) was evident in lomustine-treated U87-MG cells, although this activation did not appear to be dependent on DHA supplementation. Additionally, lomustine-treated cells' growth arrested in the G2/M cell cycle stage, regardless of the presence of DHA. Similar to the U87-MG observations, the combination of DHA and lomustine resulted in growth inhibition of 2 additional human-derived glioblastoma cell lines, DB029 and MHBT161. Importantly, in primary human-derived cerebral cortex endothelial cells, this combination was only growth inhibitory (40.8%) at the highest dose screened (100 μM), which indicates a certain degree of selectivity toward glioblastoma. CONCLUSIONS Taken together, these data suggest a potential role for a combination therapy of lomustine and DHA for the treatment of glioblastomas.

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