THER-04. IS THERE A ROLE FOR CANNABIDIOL IN THE TREATMENT OF CHILDHOOD BRAIN TUMOURS?

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 22; no. Supplement_3; p. iii472
• Main Authors: Lockwood, George, Hatfield, Amelia, Mabrouk, Mohamed, O’Sullivan, Saoirse E, Grundy, Richard G, Storer, Lisa C D
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 04.12.2020
• Subjects: Viral/Gene Therapy and other Novel Therapies
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noaa222.854

Abstract Brain tumours are the leading cause of cancer related death in children with limited treatment options and high recurrence rates. Recent evidence suggests there may be anti-tumoral properties of cannabinoids, and of cannabidiol (CBD) in particular. We evaluated the effect of CBD on paediatric brain tumour cell lines in 2D and 3D spheroids; pHGG (SF188), ependymoma (BxD-1425EPN) and human astrocytes. At the CBD EC50 concentration, astrocytic cell death was insignificant. 3D spheroids decreased in size by approximately 20% when cultured in CBD compared to cells only after 5-day exposure. Cell death increased with time after a single dose of CBD. Western Blot showed an increase in Lc3b expression (autophagy) after 24 hours incubation (early cell death) with CBD in both BxD-1425EPN and SF188 with PARP expression (apoptosis) increased after 5 days incubation (late cell death). Cell cycle analysis showed a decrease of cells in G1 and no change in G2 indicating cell cycle arrest. In hypoxia, SF188 and BxD-1425EPN cells showed decreased cell death after 24 hours and 5 days when compared to normoxia and an EC50 within acceptable limits could not be achieved. SF188 cells pre-treated with receptor antagonists indicate that CBD was not acting through CB1, CB2, GPR18, PPARα or PPARγ receptors but may act as a partial agonist of the TRPV1 and 5-HT1A receptors and a full agonist of the GPR55 receptor (resazurin assay). This provides evidence that CBD is effective at killing paediatric brain tumour cells and does not have a significant effect on normal astrocytes.