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Volume 12
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10.3390/cancers12041038
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Communication

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

by
Natasha Irrera
1,
Angela D’Ascola
1,
Giovanni Pallio
1,
Alessandra Bitto
1,
Federica Mannino
1,
Vincenzo Arcoraci
1,
Michelangelo Rottura
1,
Antonio Ieni
2,
Letteria Minutoli
1,
Daniela Metro
3,
Mario Vaccaro
1,
Domenica Altavilla
3 and
Francesco Squadrito
1,*
1
Department of Clinical and Experimental Medicine, University of Messina, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy
2
Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy
3
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 1038; https://doi.org/10.3390/cancers12041038
Submission received: 13 April 2020 / Revised: 18 April 2020 / Accepted: 20 April 2020 / Published: 23 April 2020
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Abstract

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.
Keywords: glioblastoma; β-caryophyllene; CB2 receptor; apoptosis; inflammation glioblastoma; β-caryophyllene; CB2 receptor; apoptosis; inflammation

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MDPI and ACS Style

Irrera, N.; D’Ascola, A.; Pallio, G.; Bitto, A.; Mannino, F.; Arcoraci, V.; Rottura, M.; Ieni, A.; Minutoli, L.; Metro, D.; et al. β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells. Cancers 2020, 12, 1038. https://doi.org/10.3390/cancers12041038

AMA Style

Irrera N, D’Ascola A, Pallio G, Bitto A, Mannino F, Arcoraci V, Rottura M, Ieni A, Minutoli L, Metro D, et al. β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells. Cancers. 2020; 12(4):1038. https://doi.org/10.3390/cancers12041038

Chicago/Turabian Style

Irrera, Natasha, Angela D’Ascola, Giovanni Pallio, Alessandra Bitto, Federica Mannino, Vincenzo Arcoraci, Michelangelo Rottura, Antonio Ieni, Letteria Minutoli, Daniela Metro, and et al. 2020. "β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells" Cancers 12, no. 4: 1038. https://doi.org/10.3390/cancers12041038

APA Style

Irrera, N., D’Ascola, A., Pallio, G., Bitto, A., Mannino, F., Arcoraci, V., Rottura, M., Ieni, A., Minutoli, L., Metro, D., Vaccaro, M., Altavilla, D., & Squadrito, F. (2020). β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells. Cancers, 12(4), 1038. https://doi.org/10.3390/cancers12041038

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