Title: | The cytotoxic effects of cannabidiol and cannabigerol on glioblastoma stem cells may mostly involve GPR55 and TRPV1 signalling |
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Authors: | ID Lah Turnšek, Tamara (Author) ID Majc, Bernarda (Author) ID Novak, Metka (Author) ID Sušnik, Ajda (Author) ID Breznik, Barbara (Author) ID Porčnik, Andrej (Author) ID Bošnjak, Roman (Author) ID Sadikov, Aleksander (Author) ID Malavolta, Marta (Author) ID Halilčević, Selma (Author) ID Mlakar, Jernej (Author) ID Zomer, Roby (Author) |
Files: | URL - Source URL, visit https://doi.org/10.3390/cancers14235918
PDF - Presentation file, download (2,73 MB) MD5: EB7FD0434EAEEA9645FC0BBDB0078A92
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Language: | English |
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Typology: | 1.01 - Original Scientific Article |
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Organization: | NIB - National Institute of Biology
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Abstract: | Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60–70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion receptor protein transporters TRPs. First, we found up-regulated CNR1, GPR55, and TRPV1 expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples. CNR1 and GPR55 did not correlate with glioma grade, whereas TRPV1 negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of TRPV1. With respect to markers of GBM stem cells, preferred targets of therapy, TRPV1 and GPR55, but not CNR1, strongly correlated with different sets of stemness gene markers: NOTCH, OLIG2, CD9, TRIM28, and TUFM and CD15, SOX2, OCT4, and ID1, respectively. This is in line with the higher expression of TRPV1 and GPR55 genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy. |
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Keywords: | glioblastoma, glioma, cannabigerol, cannabidiol, cannabinoid receptors, stem cells |
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Publication status: | Published |
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Publication version: | Version of Record |
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Publication date: | 30.11.2022 |
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Year of publishing: | 2022 |
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Number of pages: | str. 1-21 |
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Numbering: | Vol. 14, iss. 23 |
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PID: | 20.500.12556/DiRROS-19377 |
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UDC: | 576 |
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ISSN on article: | 2072-6694 |
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DOI: | 10.3390/cancers14235918 |
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COBISS.SI-ID: | 132774659 |
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Note: | Nasl. z nasl. zaslona;
Opis vira z dne 7. 12. 2022;
Ostali avtorji: Bernarda Majc, Metka Novak, Ajda Sušnik, Barbara Breznik, Andrej Porčnik, Roman Bošnjak, Aleksander Sadikov, Marta Malavolta, Selma Halilčević, Jernej Mlakar and Roby Zomer;
Št. članka: 5918;
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Publication date in DiRROS: | 18.07.2024 |
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Views: | 313 |
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Downloads: | 202 |
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