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

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 pote...

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Main Authors: Guya Diletta Marconi, Marialucia Gallorini, Simone Carradori, Paolo Guglielmi, Amelia Cataldi, Susi Zara
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/10/2005
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author Guya Diletta Marconi
Marialucia Gallorini
Simone Carradori
Paolo Guglielmi
Amelia Cataldi
Susi Zara
author_facet Guya Diletta Marconi
Marialucia Gallorini
Simone Carradori
Paolo Guglielmi
Amelia Cataldi
Susi Zara
author_sort Guya Diletta Marconi
collection DOAJ
description Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I&#8722;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, Cmp<b>3</b> and Cmp<b>5</b>, 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 Cmp<b>3</b> and Cmp<b>5</b> 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. Cmp<b>5</b> 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.
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spelling doaj.art-1149d031ec6f45ecb21f14218cbcc8ad2022-12-21T17:57:57ZengMDPI AGMolecules1420-30492019-05-012410200510.3390/molecules24102005molecules24102005The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma TreatmentGuya Diletta Marconi0Marialucia Gallorini1Simone Carradori2Paolo Guglielmi3Amelia Cataldi4Susi Zara5Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, ItalyDepartment of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyGliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I&#8722;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, Cmp<b>3</b> and Cmp<b>5</b>, 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 Cmp<b>3</b> and Cmp<b>5</b> 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. Cmp<b>5</b> 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.https://www.mdpi.com/1420-3049/24/10/2005GlioblastomaMAO-B inhibitorsoxidative stressmigration
spellingShingle Guya Diletta Marconi
Marialucia Gallorini
Simone Carradori
Paolo Guglielmi
Amelia Cataldi
Susi Zara
The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment
Molecules
Glioblastoma
MAO-B inhibitors
oxidative stress
migration
title The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment
title_full The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment
title_fullStr The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment
title_full_unstemmed The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment
title_short The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment
title_sort up regulation of oxidative stress as a potential mechanism of novel mao b inhibitors for glioblastoma treatment
topic Glioblastoma
MAO-B inhibitors
oxidative stress
migration
url https://www.mdpi.com/1420-3049/24/10/2005
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