ECE2024 Eposter Presentations Endocrine-Related Cancer (90 abstracts)
Opposing effects of cannabidiol (CBD) on pheochromocytoma/paraganglioma and neuroendocrine tumor cell lines and individual patient-derived primary cultures
Katharina Wang 1 , Laura Schober 1 , Alessa Fischer 2 , Nicole Bechmann 3 , Julian Maurer 1 , Lea Peischer 1 , Astrid Reul 2 , Constanze Hantel 2,4 , Martin Reincke 1 , Felix Beuschlein 1,2,5 , Mercedes Robledo 6,7 , Hermine Mohr 8 , Natalia Pellegata 8,9 , Katharina Schilbach 1 , Thomas Knösel 10,11 , Matthias Ilmer 11,12 , Martin Angele 11,12 , Matthias Kroiss 1,13 , Umberto Maccio 14 , Martina Broglie-Däppen 15 , Diana Vetter 16 , Kuno Lehmann 16 , Karel Pacak 17 , Ashley Grossman 18,19 , Christoph Auernhammer 1,11 , Kathrin Zitzmann 1 & Svenja Nölting 1,2
1LMU University Hospital, Department of Internal Medicine IV, Munich, Germany; 2University Hospital Zurich (USZ) and University of Zurich (UZH), Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland; 3University Hospital Carl Gustav Carus, Institute of Clinical Chemistry and Laboratory Medicine, Dresden, Germany; 4University Hospital Carl Gustav Carus Dresden, Department of Internal Medicine III, Dresden, Germany; 5The LOOP Zurich - Medical Research Center, Zurich, Switzerland; 6Spanish National Cancer Research Center (CNIO), Hereditary Endocrine Cancer Group, Madrid, Spain; 7Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain; 8Helmholtz Center Munich, Institute for Diabetes and Cancer (IDC), Munich, Germany; 9University of Pavia, Department of Biology and Biotechnology, Pavia, Italy; 10Faculty of Medicine, LMU Munich, Institue of Pathology, Munich, Germany; 11LMU University Hospital, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), Munich, Germany; 12LMU University Hospital, Department of General, Visceral, and Transplantation Surgery, Munich, Germany; 13University Hospital Würzburg, Department of Medicine I, Division of Endocrinology and Diabetes, Würzburg, Germany; 14University Hospital Zurich, Department of Pathology and Molecular Pathology, Zurich, Switzerland; 15University Hospital Zurich, Department of Otorhinolaryngology, Head and Neck Surgery, Zurich, Switzerland; 16University Hospital Zurich, Department of Visceral and Transplantation Surgery, Zurich, Switzerland; 17Eunice Kennedy Shriver NICHD, Bethesda, United States; 18University of Oxford, Green Templeton College, Oxford, United Kingdom; 19Royal Free Hospital, NET Unit, ENETS Centre of Excellence, London, United Kingdom
The recreational use of cannabis is becoming more widespread since many countries, including parts of Europe, are currently discussing legalisation. Moreover, the medical use of cannabinoids is already established and has many indications such as multiple sclerosis-induced spasticity or supportive therapy in the case of tumour-associated pain or loss of weight or appetite. However, the effects of cannabinoids on tumour growth still remain largely unexplored in many tumour entities, including phaeochromocytomas and paragangliomas (PPGLs), and neuroendocrine tumours (NETs). Therefore, we have now evaluated the effects of cannabidiol (CBD) in PPGL/NET cell lines, a PPGL 3D spheroid model and, most importantly, in patient-derived PPGL/NET primary cultures. In the PPGL cell lines (MPC, MTT) and in some NET cell lines (BON1, NCI-H727), CBD showed significant anti-tumour effects. Similarly, CBD also showed efficacy in PPGL (MPC) 3D spheroids, leading to a significant reduction in spheroid diameter. However, in a human pancreatic NET cell line (QGP1) we found significant tumour-promoting effects – thus demonstrating overall opposing effects of CBD on cell viability in different cell lines. Due to these results, we also validated these data in individual human primary cultures derived from patients with PPGLs (n=35) and NETs (n=11) and confirmed the opposing effects induced by CBD. In clinically relevant doses, we found significant anti-tumour effects in 14% and significant tumour-promoting effects in 17% of PPGLs. These effects were more pronounced using slightly higher doses of CBD, leading to significant anti-tumour effects in 27% and significant tumour-promoting effects in 18% of both PPGLs and NETs. Moreover, we performed genetic testing of individual PPGLs, which allowed us to evaluate cluster-dependent drug responsivity: In the cluster 2-associated PPGLs we found a significantly stronger CBD-induced cell viability reduction compared to the cluster 1-associated PPGLs. In conclusion, we offer clinically relevant data on a potential novel treatment option for PPGLs and NETs, particularly regarding personalised therapy in cluster 2-associated PPGLs, but also evidence for potential tumour-promoting effects of CBD in some PPGLs and NETs. Therefore, caution may be needed when treating PPGL or NET patients with cannabinoids as supportive therapies or even possibly as health supplements
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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