Journal article
Assessment of cannabidiol and Δ9-Tetrahydrocannabiol in mouse models of Medulloblastoma and Ependymoma
Cancers, Vol.13(2), Art. 330
2021
Abstract
Children with medulloblastoma and ependymoma are treated with a multidisciplinary approach that incorporates surgery, radiotherapy, and chemotherapy; however, overall survival rates for patients with high-risk disease remain unsatisfactory. Data indicate that plant-derived cannabinoids are effective against adult glioblastoma; however, preclinical evidence supporting their use in pediatric brain cancers is lacking. Here we investigated the potential role for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in medulloblastoma and ependymoma. Dose-dependent cytotoxicity of medulloblastoma and ependymoma cells was induced by THC and CBD in vitro, and a synergistic reduction in viability was observed when both drugs were combined. Mechanistically, cannabinoids induced cell cycle arrest, in part by the production of reactive oxygen species, autophagy, and apoptosis; however, this did not translate to increased survival in orthotopic transplant models despite being well tolerated. We also tested the combination of cannabinoids with the medulloblastoma drug cyclophosphamide, and despite some in vitro synergism, no survival advantage was observed in vivo. Consequently, clinical benefit from the use of cannabinoids in the treatment of high-grade medulloblastoma and ependymoma is expected to be limited. This study emphasizes the importance of preclinical models in validating therapeutic agent efficacy prior to clinical trials, ensuring that enrolled patients are afforded the most promising therapies available.
Details
- Title
- Assessment of cannabidiol and Δ9-Tetrahydrocannabiol in mouse models of Medulloblastoma and Ependymoma
- Authors/Creators
- C. Andradas (Author/Creator) - The Kids Research Institute AustraliaJ. Byrne (Author/Creator) - The Kids Research Institute AustraliaM. Kuchibhotla (Author/Creator) - The Kids Research Institute AustraliaM. Ancliffe (Author/Creator) - The Kids Research Institute AustraliaA.C. Jones (Author/Creator) - The Kids Research Institute AustraliaB. Carline (Author/Creator) - The Kids Research Institute AustraliaH. Hii (Author/Creator) - The Kids Research Institute AustraliaA. Truong (Author/Creator) - The Kids Research Institute AustraliaL.C.D. Storer (Author/Creator) - Brain Tumour ResearchT.A. Ritzmann (Author/Creator) - Brain Tumour ResearchR.G. Grundy (Author/Creator) - Brain Tumour ResearchN.G. Gottardo (Author/Creator) - The Kids Research Institute AustraliaR. Endersby (Author/Creator) - The University of Western Australia
- Publication Details
- Cancers, Vol.13(2), Art. 330
- Publisher
- MDPI AG
- Identifiers
- 991005545250907891
- Copyright
- © 2021 MDPI.
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
122 File views/ downloads
27 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.100 Substance Abuse
- 1.100.625 Cannabinoids
- Web Of Science research areas
- Oncology
- ESI research areas
- Clinical Medicine