Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells
Over the last few years, much attention has been paid to phytocannabinoids derived from Cannabis for their therapeutic potential. Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC) and cannabidiol (CBD) are the most abundant compounds of the <i>Cannabis sativa L.<...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/18/5576 |
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| author | Maria Salbini Alessandra Quarta Fabiana Russo Anna Maria Giudetti Cinzia Citti Giuseppe Cannazza Giuseppe Gigli Daniele Vergara Antonio Gaballo |
| author_facet | Maria Salbini Alessandra Quarta Fabiana Russo Anna Maria Giudetti Cinzia Citti Giuseppe Cannazza Giuseppe Gigli Daniele Vergara Antonio Gaballo |
| author_sort | Maria Salbini |
| collection | DOAJ |
| description | Over the last few years, much attention has been paid to phytocannabinoids derived from Cannabis for their therapeutic potential. Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC) and cannabidiol (CBD) are the most abundant compounds of the <i>Cannabis sativa L.</i> plant. Recently, novel phytocannabinoids, such as cannabidibutol (CBDB) and cannabidiphorol (CBDP), have been discovered. These new molecules exhibit the same terpenophenolic core of CBD and differ only for the length of the alkyl side chain. Roles of CBD homologs in physiological and pathological processes are emerging but the exact molecular mechanisms remain to be fully elucidated. Here, we investigated the biological effects of the newly discovered CBDB or CBDP, compared to the well-known natural and synthetic CBD (nat CBD and syn CBD) in human breast carcinoma cells that express CB receptors. In detail, our data demonstrated that the treatment of cells with the novel phytocannabinoids affects cell viability, increases the production of reactive oxygen species (ROS) and activates cellular pathways related to ROS signaling, as already demonstrated for natural CBD. Moreover, we observed that the biological activity is significantly increased upon combining CBD homologs with drugs that inhibit the activity of enzymes involved in the metabolism of endocannabinoids, such as the monoacylglycerol lipase (MAGL) inhibitor, or with drugs that induces the activation of cellular stress pathways, such as the phorbol ester 12-myristate 13-acetate (PMA). |
| first_indexed | 2024-03-10T07:24:11Z |
| format | Article |
| id | doaj.art-715711a8a9844780aed2a9b10bbbd242 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T07:24:11Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-715711a8a9844780aed2a9b10bbbd2422023-11-22T14:25:14ZengMDPI AGMolecules1420-30492021-09-012618557610.3390/molecules26185576Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer CellsMaria Salbini0Alessandra Quarta1Fabiana Russo2Anna Maria Giudetti3Cinzia Citti4Giuseppe Cannazza5Giuseppe Gigli6Daniele Vergara7Antonio Gaballo8CNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, ItalyCNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, ItalyClinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, 73100 Lecce, ItalyCNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, ItalyCNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, ItalyCNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, 73100 Lecce, ItalyCNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, ItalyOver the last few years, much attention has been paid to phytocannabinoids derived from Cannabis for their therapeutic potential. Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC) and cannabidiol (CBD) are the most abundant compounds of the <i>Cannabis sativa L.</i> plant. Recently, novel phytocannabinoids, such as cannabidibutol (CBDB) and cannabidiphorol (CBDP), have been discovered. These new molecules exhibit the same terpenophenolic core of CBD and differ only for the length of the alkyl side chain. Roles of CBD homologs in physiological and pathological processes are emerging but the exact molecular mechanisms remain to be fully elucidated. Here, we investigated the biological effects of the newly discovered CBDB or CBDP, compared to the well-known natural and synthetic CBD (nat CBD and syn CBD) in human breast carcinoma cells that express CB receptors. In detail, our data demonstrated that the treatment of cells with the novel phytocannabinoids affects cell viability, increases the production of reactive oxygen species (ROS) and activates cellular pathways related to ROS signaling, as already demonstrated for natural CBD. Moreover, we observed that the biological activity is significantly increased upon combining CBD homologs with drugs that inhibit the activity of enzymes involved in the metabolism of endocannabinoids, such as the monoacylglycerol lipase (MAGL) inhibitor, or with drugs that induces the activation of cellular stress pathways, such as the phorbol ester 12-myristate 13-acetate (PMA).https://www.mdpi.com/1420-3049/26/18/5576MCF-7cannabidiolROSoxidative stressautophagyaltered mitochondria |
| spellingShingle | Maria Salbini Alessandra Quarta Fabiana Russo Anna Maria Giudetti Cinzia Citti Giuseppe Cannazza Giuseppe Gigli Daniele Vergara Antonio Gaballo Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells Molecules MCF-7 cannabidiol ROS oxidative stress autophagy altered mitochondria |
| title | Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells |
| title_full | Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells |
| title_fullStr | Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells |
| title_full_unstemmed | Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells |
| title_short | Oxidative Stress and Multi-Organel Damage Induced by Two Novel Phytocannabinoids, CBDB and CBDP, in Breast Cancer Cells |
| title_sort | oxidative stress and multi organel damage induced by two novel phytocannabinoids cbdb and cbdp in breast cancer cells |
| topic | MCF-7 cannabidiol ROS oxidative stress autophagy altered mitochondria |
| url | https://www.mdpi.com/1420-3049/26/18/5576 |
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