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AuthorMannino, Federica
AuthorPallio, Giovanni
AuthorCorsaro, Roberta
AuthorMinutoli, Letteria
AuthorAltavilla, Domenica
AuthorVermiglio, Giovanna
AuthorAllegra, Alessandro
AuthorEid, Ali H.
AuthorBitto, Alessandra
AuthorSquadrito, Francesco
AuthorIrrera, Natasha
Available date2023-07-27T06:48:45Z
Publication Date2021-11-16
Publication NameCancers
Identifierhttp://dx.doi.org/10.3390/cancers13225741
CitationMannino, F., Pallio, G., Corsaro, R., Minutoli, L., Altavilla, D., Vermiglio, G., ... & Irrera, N. (2021). Beta-caryophyllene exhibits anti-proliferative effects through apoptosis induction and cell cycle modulation in multiple myeloma cells. Cancers, 13(22), 5741.
ISSN2072-6694
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85119055067&origin=inward
URIhttp://hdl.handle.net/10576/46359
AbstractCannabinoid receptors, which are widely distributed in the body, have been considered as possible pharmacological targets for the management of several tumors. Cannabinoid type 2 receptors (CB2Rs) belong to the G protein-coupled receptor family and are mainly expressed in hematopoietic and immune cells, such as B-cells, T-cells, and macrophages; thus, CB2R activation might be useful for treating cancers affecting plasma cells, such as multiple myeloma (MM). Previous studies have shown that CB2R stimulation may have anti-proliferative effects; therefore, the purpose of the present study was to explore the antitumor effect of beta-caryophyllene (BCP), a CB2R agonist, in an in vitro model of MM. Dexamethasone-resistant (MM.1R) and sensitive (MM.1S) human multiple myeloma cell lines were used in this study. Cells were treated with different concentrations of BCP for 24 h, and a group of cells was pre-incubated with AM630, a specific CB2R antagonist. BCP treatment reduced cell proliferation through CB2R stimulation; notably, BCP considerably increased the pro-apoptotic protein Bax and decreased the anti-apoptotic molecule Bcl-2. Furthermore, an increase in caspase 3 protein levels was detected following BCP incubation, thus demonstrating its anti-proliferative effect through apoptosis activation. In addition, BCP regulated AKT, Wnt1, and beta-catenin expression, showing that CB2R stimulation may decrease cancer cell proliferation by modulating Wnt/β-catenin signaling. These effects were counteracted by AM630 co-incubation, thus confirming that BCP’s mechanism of action is mainly related to CB2R modulation. A decrease in β-catenin regulated the impaired cell cycle and especially promoted cyclin D1 and CDK 4/6 reduction. Taken together, these data revealed that BCP might have significant and effective anti-cancer and anti-proliferative effects in MM cells by activating apoptosis, modulating different molecular pathways, and downregulating the cell cycle.
Languageen
PublisherMultidisciplinary Digital Publishing Institute (MDPI)
SubjectApoptosis
Beta-caryophyllene
Cannabinoid receptor 2
Multiple myeloma
Wnt/β-catenin
TitleBeta-caryophyllene exhibits anti-proliferative effects through apoptosis induction and cell cycle modulation in multiple myeloma cells
TypeArticle
Issue Number22
Volume Number13
dc.accessType Open Access


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