Abstract
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.
Highlights
Gliomas are the first brain tumors assumed to originate from the neuroglial stem or from progenitor cells, characterized by inappropriate proliferation, infiltration into neighboring normal brain tissue and the disruption of the normal functioning of the brain
The effects of Compound 3 (Cmp3) and Cmp5 were evaluated by means of MTT assay on rat C6 glioma cell line compared with non-tumoral CTX
0.0002, ** p < 0.0005, * p < 0.005. It is widely reported in scientific literature that the Monoamine Oxidase B (MAO-B) activity appears to increase with agingItasiswell as inreported patients in affected by neurodegenerative including widely scientific literature that the conditions
Summary
Gliomas are the first brain tumors assumed to originate from the neuroglial stem or from progenitor cells, characterized by inappropriate proliferation, infiltration into neighboring normal brain tissue and the disruption of the normal functioning of the brain. Based on their histological appearance, gliomas are conventionally classified as astrocytic, oligodendroglial or ependymal tumors and attributed by the. Glioblastoma (GBM), a grade IV astrocytoma notoriously treatment–resistant brain cancer, is the greatest destructive brain tumor, largely due to the limited effects of conventional post-surgical chemotherapeutic agents and to irradiation [2]. The present therapies for high-grade gliomas are not an effective approach; after preliminary diagnosis, patients receive a maximal surgical resection, concomitant radiotherapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
