Title: | Synthetic cannabinoid WIN 55,212–2 inhibits growth and induces cell death of oral and pancreatic stem-like/poorly differentiated tumor cells |
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Authors: | ID Ko, Meng-Wei (Author) ID Breznik, Barbara (Author) ID Senjor, Emanuela (Author) ID Jewett, Anahid (Author) |
Files: | URL - Source URL, visit https://doi.org/10.1016/j.adcanc.2022.100043
PDF - Presentation file, download (8,37 MB) MD5: 8BB1161F766362CA48EE4276CE48335F
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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: | We report here that synthetic cannabinoid WIN 55,212–2 inhibits tumor cell proliferation and induces cell death of oral and pancreatic tumor cells, and the effect is much more pronounced on stem-like/poorly differentiated OSCSCs and MP2 cells when compared to well-differentiated OSCCs, and PL-12 tumor cells. In addition, WIN 55,212-2 decreases cell surface expression of CD44, CD54, MHC class I and PD-L1 on oral and pancreatic tumor cells with the exception of PD-L1 expression on well-differentiated PL-12 pancreatic tumor cells which exhibits an increase in the expression rather than a decrease. Overall, we demonstrate that WIN 55,212-2 has an increased targeting activity against cancer stem cells/poorly differentiated oral and pancreatic tumor cells when compared to well-differentiated tumor cells, and furthermore, such differences in function do not correlate with the levels of CB1 and CB2 receptor expression on tumor cells, suggesting it's function either through post-receptor mediated activation and/or yet-to-be identified novel receptors. Intraperitoneal (IP) delivery of WIN 55-212-2 in humanized BLT mice is found to impart an activating potential for NK cells demonstrating increased NK cell mediated cytotoxicity and secretion of IFN-γ in our preliminary experiments. These results not only suggest a direct targeting of CSCs/poorly differentiated tumors by WIN 55-212-2 but also by indirect targeting of such tumors through the activation and increased functions of NK cells. |
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Keywords: | cancer stem cells, cannabinoids, cell death, cancer biology, genetic toxicology |
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Publication status: | Published |
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Publication version: | Version of Record |
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Publication date: | 01.10.2022 |
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Year of publishing: | 2022 |
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Number of pages: | str. [1]-10 |
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Numbering: | Vol. 5 |
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PID: | 20.500.12556/DiRROS-19322 |
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UDC: | 575 |
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ISSN on article: | 2667-3940 |
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DOI: | 10.1016/j.adcanc.2022.100043 |
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COBISS.SI-ID: | 113550595 |
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Note: | Ostali avtorji: Barbara Breznik, Emanuela Senjor, Anahid Jewett;
Nasl. z nasl. zaslona;
Opis vira z dne 1. 7. 2022;
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Publication date in DiRROS: | 17.07.2024 |
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Views: | 318 |
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Downloads: | 187 |
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