THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner
Glioblastoma (GBM) is the most frequent malignant tumor of the central nervous system in humans with a median survival time of less than 15 months. ∆<sup>9</sup>-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best-characterized components of <i>Cannabis sativa</i> p...
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/5/1064 |
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| author | Marc Richard Kolbe Tim Hohmann Urszula Hohmann Chalid Ghadban Ken Mackie Christin Zöller Julian Prell Jörg Illert Christian Strauss Faramarz Dehghani |
| author_facet | Marc Richard Kolbe Tim Hohmann Urszula Hohmann Chalid Ghadban Ken Mackie Christin Zöller Julian Prell Jörg Illert Christian Strauss Faramarz Dehghani |
| author_sort | Marc Richard Kolbe |
| collection | DOAJ |
| description | Glioblastoma (GBM) is the most frequent malignant tumor of the central nervous system in humans with a median survival time of less than 15 months. ∆<sup>9</sup>-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best-characterized components of <i>Cannabis sativa</i> plants with modulating effects on cannabinoid receptors 1 and 2 (CB<sub>1</sub> and CB<sub>2</sub>) and on orphan receptors such as GPR18 or GPR55. Previous studies have demonstrated anti-tumorigenic effects of THC and CBD in several tumor entities including GBM, mostly mediated via CB<sub>1</sub> or CB<sub>2</sub>. In this study, we investigated the non-CB<sub>1</sub>/CB<sub>2</sub> effects of THC on the cell cycle of GBM cells isolated from human tumor samples. Cell cycle entry was measured after 24 h upon exposure by immunocytochemical analysis of Ki67 as proliferation marker. The Ki67-reducing effect of THC was abolished in the presence of CBD, whereas CBD alone did not cause any changes. To identify the responsible receptor for THC effects, we first characterized the cells regarding their expression of different cannabinoid receptors: CB<sub>1</sub>, CB<sub>2</sub>, GPR18, and GPR55. Secondly, the receptors were pharmacologically blocked by application of their selective antagonists AM281, AM630, O-1918, and CID16020046 (CID), respectively. All examined cells expressed the receptors, but only in presence of the GPR55 antagonist CID was the THC effect diminished. Stimulation with the GPR55 agonist lysophosphatidylinositol (LPI) revealed similar effects as obtained for THC. The LPI effects were also inhibited by CBD and CID, confirming a participation of GPR55 and suggesting its involvement in modifying the cell cycle of patient-derived GBM cells. |
| first_indexed | 2024-03-09T05:53:42Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:53:42Z |
| publishDate | 2021-03-01 |
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| series | Cancers |
| spelling | doaj.art-db35ef99a5b9402894f11f0ec1f04cb12023-12-03T12:15:56ZengMDPI AGCancers2072-66942021-03-01135106410.3390/cancers13051064THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent MannerMarc Richard Kolbe0Tim Hohmann1Urszula Hohmann2Chalid Ghadban3Ken Mackie4Christin Zöller5Julian Prell6Jörg Illert7Christian Strauss8Faramarz Dehghani9Department of Anatomy and Cell Biology, Medical Faculty of Martin-Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyDepartment of Anatomy and Cell Biology, Medical Faculty of Martin-Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyDepartment of Anatomy and Cell Biology, Medical Faculty of Martin-Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyDepartment of Anatomy and Cell Biology, Medical Faculty of Martin-Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyDepartment of Psychological & Brain Sciences, Indiana University, 1101E. 10th, Bloomington, IN 47405, USADepartment of Neurosurgery, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyDepartment of Neurosurgery, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyDepartment of Neurosurgery, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyDepartment of Neurosurgery, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120 Halle (Saale), GermanyDepartment of Anatomy and Cell Biology, Medical Faculty of Martin-Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyGlioblastoma (GBM) is the most frequent malignant tumor of the central nervous system in humans with a median survival time of less than 15 months. ∆<sup>9</sup>-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best-characterized components of <i>Cannabis sativa</i> plants with modulating effects on cannabinoid receptors 1 and 2 (CB<sub>1</sub> and CB<sub>2</sub>) and on orphan receptors such as GPR18 or GPR55. Previous studies have demonstrated anti-tumorigenic effects of THC and CBD in several tumor entities including GBM, mostly mediated via CB<sub>1</sub> or CB<sub>2</sub>. In this study, we investigated the non-CB<sub>1</sub>/CB<sub>2</sub> effects of THC on the cell cycle of GBM cells isolated from human tumor samples. Cell cycle entry was measured after 24 h upon exposure by immunocytochemical analysis of Ki67 as proliferation marker. The Ki67-reducing effect of THC was abolished in the presence of CBD, whereas CBD alone did not cause any changes. To identify the responsible receptor for THC effects, we first characterized the cells regarding their expression of different cannabinoid receptors: CB<sub>1</sub>, CB<sub>2</sub>, GPR18, and GPR55. Secondly, the receptors were pharmacologically blocked by application of their selective antagonists AM281, AM630, O-1918, and CID16020046 (CID), respectively. All examined cells expressed the receptors, but only in presence of the GPR55 antagonist CID was the THC effect diminished. Stimulation with the GPR55 agonist lysophosphatidylinositol (LPI) revealed similar effects as obtained for THC. The LPI effects were also inhibited by CBD and CID, confirming a participation of GPR55 and suggesting its involvement in modifying the cell cycle of patient-derived GBM cells.https://www.mdpi.com/2072-6694/13/5/1064brain tumorglioblastomaTHCCBDcannabidiolCB<sub>1</sub> |
| spellingShingle | Marc Richard Kolbe Tim Hohmann Urszula Hohmann Chalid Ghadban Ken Mackie Christin Zöller Julian Prell Jörg Illert Christian Strauss Faramarz Dehghani THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner Cancers brain tumor glioblastoma THC CBD cannabidiol CB<sub>1</sub> |
| title | THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner |
| title_full | THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner |
| title_fullStr | THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner |
| title_full_unstemmed | THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner |
| title_short | THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner |
| title_sort | thc reduces ki67 immunoreactive cells derived from human primary glioblastoma in a gpr55 dependent manner |
| topic | brain tumor glioblastoma THC CBD cannabidiol CB<sub>1</sub> |
| url | https://www.mdpi.com/2072-6694/13/5/1064 |
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