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β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells
Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PP...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226353/ https://www.ncbi.nlm.nih.gov/pubmed/32340197 http://dx.doi.org/10.3390/cancers12041038 |
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author | Irrera, Natasha D’Ascola, Angela Pallio, Giovanni Bitto, Alessandra Mannino, Federica Arcoraci, Vincenzo Rottura, Michelangelo Ieni, Antonio Minutoli, Letteria Metro, Daniela Vaccaro, Mario Altavilla, Domenica Squadrito, Francesco |
author_facet | Irrera, Natasha D’Ascola, Angela Pallio, Giovanni Bitto, Alessandra Mannino, Federica Arcoraci, Vincenzo Rottura, Michelangelo Ieni, Antonio Minutoli, Letteria Metro, Daniela Vaccaro, Mario Altavilla, Domenica Squadrito, Francesco |
author_sort | Irrera, Natasha |
collection | PubMed |
description | Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP’s anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCP may act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK. |
format | Online Article Text |
id | pubmed-7226353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72263532020-05-18 β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells Irrera, Natasha D’Ascola, Angela Pallio, Giovanni Bitto, Alessandra Mannino, Federica Arcoraci, Vincenzo Rottura, Michelangelo Ieni, Antonio Minutoli, Letteria Metro, Daniela Vaccaro, Mario Altavilla, Domenica Squadrito, Francesco Cancers (Basel) Communication Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP’s anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCP may act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK. MDPI 2020-04-23 /pmc/articles/PMC7226353/ /pubmed/32340197 http://dx.doi.org/10.3390/cancers12041038 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Irrera, Natasha D’Ascola, Angela Pallio, Giovanni Bitto, Alessandra Mannino, Federica Arcoraci, Vincenzo Rottura, Michelangelo Ieni, Antonio Minutoli, Letteria Metro, Daniela Vaccaro, Mario Altavilla, Domenica Squadrito, Francesco β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells |
title | β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells |
title_full | β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells |
title_fullStr | β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells |
title_full_unstemmed | β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells |
title_short | β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells |
title_sort | β-caryophyllene inhibits cell proliferation through a direct modulation of cb2 receptors in glioblastoma cells |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226353/ https://www.ncbi.nlm.nih.gov/pubmed/32340197 http://dx.doi.org/10.3390/cancers12041038 |
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