ReferenceID 1489
Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells
Cancers (Basel)
Cannabinoid 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
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- Reference Id
- 1489
- Evidence Id
- 18079
- Core Evidence Id
- 18079
- Source Reference Id
- 2989
- Herb2 Reference Id
- HBREF003786
- Subject Paper Key
- HBIN019817_34830893
- Pubmed Id
- 34830893
- Doi
- 10.3390/cancers13225741
- Paper Title
- Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells
- Paper Abstract
- Cannabinoid 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/beta-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 beta-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.
- Journal
- Cancers (Basel)
- Publish Year
- 2021
- Experiment Subject
- human; dexamethasone-resistant (mm.1r) and sensitive (mm.1s) human multiple myeloma cell lines; mm cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Cancers; Multiple Myeloma; Myeloma; Cancer; Tumors
- Paper Title Cn
- Paper Title En
- Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells
- Bilingual Status
- semi_complete