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Title:The cytotoxic effects of cannabidiol and cannabigerol on glioblastoma stem cells may mostly involve GPR55 and TRPV1 signalling
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 URL - Source URL, visit https://doi.org/10.3390/cancers14235918
 
.pdf PDF - Presentation file, download (2,73 MB)
MD5: EB7FD0434EAEEA9645FC0BBDB0078A92
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo NIB - National Institute of Biology
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.
Keywords:glioblastoma, glioma, cannabigerol, cannabidiol, cannabinoid receptors, stem cells
Publication status:Published
Publication version:Version of Record
Publication date:30.11.2022
Year of publishing:2022
Number of pages:str. 1-21
Numbering:Vol. 14, iss. 23
PID:20.500.12556/DiRROS-19377 New window
UDC:576
ISSN on article:2072-6694
DOI:10.3390/cancers14235918 New window
COBISS.SI-ID:132774659 New window
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;
Publication date in DiRROS:18.07.2024
Views:308
Downloads:198
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Record is a part of a journal

Title:Cancers
Shortened title:Cancers
Publisher:MDPI
ISSN:2072-6694
COBISS.SI-ID:517914137 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0245-2019
Name:Ekotoksiologija, toksikološka genomika in karcinogeneza

Funder:EC - European Commission
Project number:956394
Name:PremAtuRe nEwborn motor and cogNitive impairmenTs: Early diagnosis
Acronym:PARENT

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P2-0209-2022
Name:Umetna inteligenca in inteligentni sistemi

Funder:EC - European Commission
Funding programme:European Program of Cross-Border Cooperation for Slovenia-Italy Interreg
Acronym:TRANS-GLIOMA

Funder:Other - Other funder or multiple funders
Funding programme:MGC Pharmaceuticals

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

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