scholarly journals The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 2005 ◽  
Author(s):  
Guya Diletta Marconi ◽  
Marialucia Gallorini ◽  
Simone Carradori ◽  
Paolo Guglielmi ◽  
Amelia Cataldi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cell Cycle Arrest ◽  
Glioma Cells ◽  
C6 Glioma ◽  
World Health ◽  
C6 Glioma Cells ◽  
Mao B ◽  
Cycle Arrest

Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I–IV by the World Health Organization. Glioblastoma is the fastest growing and most devastating IV glioma. The aim of this paper is to evaluate the biological effects of two potent and selective Monoamine Oxidase B (MAO-B) inhibitors, Cmp3 and Cmp5, in C6 glioma cells and in CTX/TNA2 astrocytes in terms of cell proliferation, apoptosis occurrence, inflammatory events and cell migration. These compounds decrease C6 glioma cells viability sparing normal astrocytes. Cell cycle analysis, the Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) production were detected, revealing that Cmp3 and Cmp5 induce a G1 or G2/M cell cycle arrest, as well as a MMP depolarization and an overproduction of ROS; moreover, they inhibit the expression level of inducible nitric oxide synthase 2, thus contributing to fatal drug-induced oxidative stress. Cmp5 notably reduces glioma cell migration via down-regulating Matrix Metalloproteinases 2 and 9. This study demonstrated that our novel MAO-B inhibitors increase the oxidative stress level resulting in a cell cycle arrest and markedly reduces glioma cells migration thus reinforcing the hypothesis of a critical role-played by MAO-B in mediating oncogenesis in high-grade gliomas.

Epigenetic Properties of Fumonisin B1: Cell Cycle Arrest and DNA Base Modification in C6 Glioma Cells

2000 ◽  
Vol 164 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Théophile A. Mobio ◽  
Rachid Anane ◽  
Isabelle Baudrimont ◽  
Maria-Rosaria Carratú ◽  
Thomas W. Shier ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Fumonisin B1 ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Base Modification ◽  
Cycle Arrest ◽  
Dna Base

MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells and Tissue Through Cell Cycle Arrest

2018 ◽  
Vol 15 (3) ◽  
pp. 246-255 ◽  
Author(s):  
Long Zhao ◽  
Xiaoping Tang ◽  
Renguo Luo ◽  
Jie Duan ◽  
Yuanchuan Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cellular Proliferation ◽  
Glioma Cells ◽  
Cycle Arrest

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals DDRE-03. IDH1-MUTANT GBM CELLS ARE HIGHLY SENSITIVE TO COMBINATION OF KDM6A/B AND HDAC INHIBITORS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i6-i7
Author(s):  
Alişan Kayabölen ◽  
Gizem Nur Sahin ◽  
Fidan Seker ◽  
Ahmet Cingöz ◽  
Bekir Isik ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Mutant Cell ◽  
Glioma Cells ◽  
Epigenetic Therapy ◽  
Low Grade ◽  
Orthotopic Model ◽  
Cycle Arrest ◽  
Mutant Cells

Abstract Mutations in IDH1 and IDH2 genes are common in low grade gliomas and secondary GBM and are known to cause a distinct epigenetic landscape in these tumors. To interrogate the epigenetic vulnerabilities of IDH-mutant gliomas, we performed a chemical screen with inhibitors of chromatin modifiers and identified 5-azacytidine, Chaetocin, GSK-J4 and Belinostat as potent agents against primary IDH1-mutant cell lines. Testing the combinatorial efficacy of these agents, we demonstrated GSK-J4 and Belinostat combination as a very effective treatment for the IDH1-mutant glioma cells. Engineering established cell lines to ectopically express IDH1R132H, we showed that IDH1R132H cells adopted a different transcriptome with changes in stress-related pathways that were reversible with the mutant IDH1 inhibitor, GSK864. The combination of GSK-J4 and Belinostat was highly effective on IDH1R132H cells, but not on wt glioma cells or nonmalignant fibroblasts and astrocytes. The cell death induced by GSK-J4 and Belinostat combination involved the induction of cell cycle arrest and apoptosis. RNA sequencing analyses revealed activation of inflammatory and unfolded protein response pathways in IDH1-mutant cells upon treatment with GSK-J4 and Belinostat conferring increased stress to glioma cells. Specifically, GSK-J4 induced ATF4-mediated integrated stress response and Belinostat induced cell cycle arrest in primary IDH1-mutant glioma cells; which were accompanied by DDIT3/CHOP-dependent upregulation of apoptosis. Moreover, to dissect out the responsible target histone demethylase, we undertook genetic approach and demonstrated that CRISPR/Cas9 mediated ablation of both KDM6A and KDM6B genes phenocopied the effects of GSK-J4 in IDH1-mutant cells. Finally, GSK-J4 and Belinostat combination significantly decreased tumor growth and increased survival in an orthotopic model in mice. Together, these results suggest a potential combination epigenetic therapy against IDH1-mutant gliomas.

scholarly journals Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cycle arrest in MCF-7 cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (10) ◽  
pp. 101042831772618 ◽  
Author(s):  
Khuloud Bajbouj ◽  
Jasmin Shafarin ◽  
Maher Y Abdalla ◽  
Iman M Ahmad ◽  
Mawieh Hamad
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Iron Metabolism ◽  
Membrane Damage ◽  
Intracellular Iron ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

2016 ◽  
Vol 13 (2) ◽  
pp. 1007-1013 ◽  
Author(s):  
Aisha Maimaitili ◽  
Zunhua Shu ◽  
Xiaojiang Cheng ◽  
Kadeer Kaheerman ◽  
Alifu Sikandeer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Glioma Cells ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest
Sign in / Sign up

Export Citation Format

Share Document