Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Richtig, G.
Cannabinoids as a Potential Novel Therapeutic Approach to Metastatic Melanoma
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2024. pp. 136
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Heinemann Akos
- Höfler Gerald
- Pichler Martin
- Altmetrics:
- Abstract:
- Background: Cannabinoids are mainly used for recreational purpose but made their way also into oncology since these substances can be taken to increase appetite in tumour cachexia. Since, there are some hints in the literature that cannabinoids might have some anti-cancerous effects, cannabinoids are also taken by patients with metastatic disease under conventional therapy. Objectives: This study addressed the question if and how cannabinoids mediate pro-apoptotic effects in metastatic melanoma in-vivo and in-vitro and its value in comparison with conventional targeted therapy in-vivo. Methods: Several melanoma cell lines were treated with different concentrations of cannabinoids and anti-cancer efficacy was assessed by proliferation and apoptosis assays. Subsequent pathway analysis was performed using apoptosis, proliferation, flow cytometry, immunohistochemistry, cytokine array and confocal microscopy data. Efficacy of cannabinoids in combination with trametinib was studied in NSG mice in vivo. Results: Cannabinoids reduced cell viability in multiple melanoma cell lines in a dose-dependent manner. The effect was mediated by CB1, TRPV1 and PPARα receptors whereby simultaneous pharmacological blockade of all three receptors protected from cannabinoid-induced apoptosis. Cannabinoids initiated apoptosis by mitochondrial cytochrome c release with consecutive activation of different caspases. Essentially, cannabinoids significantly decreased tumour growth in vivo and were as potent as the clinically used MEK inhibitor trametinib. Conclusions: We could demonstrate that cannabinoids reduce cell viability in several melanoma cell lines, initiate apoptosis via the intrinsic apoptotic pathway by cytochrome c release and caspase activation and do not interfere with commonly used targeted therapy.