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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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