http://mct.aacrjournals.org/content/early/2014/11/12/1535-7163.MCT-14-0402.abstract
The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model
+ Author Affiliations
- ↵*Corresponding Author:
Wai Liu, Department of Oncology, Division of Clinical Sciences, St George's, University of London, Second Floor, Jenner Wing, London, SW17 0RE, United Kingdom. Phone: 44-20-8725-5037; Fax: 44-20-8725-0158; E-mail: w.liu@sgul.ac.uk 
Abstract
High-grade glioma is one of the most 
aggressive cancers in adult humans and long-term survival rates are very
 low as standard
                     treatments for glioma remain largely unsuccessful. 
Cannabinoids have been shown to specifically inhibit glioma growth as 
well
                     as neutralize oncogenic processes such as 
angiogenesis. In an attempt to improve treatment outcome, we have 
investigated the
                     effect of Δ9-tetrahydrocannabinol (THC) 
and cannabidiol (CBD) both alone and in combination with radiotherapy in
 a number of glioma cell
                     lines (T98G, U87MG, and GL261). Cannabinoids were 
used in two forms, pure (P) and as a botanical drug substance (BDS). 
Results
                     demonstrated a duration- and dose-dependent 
reduction in cell viability with each cannabinoid and suggested that 
THC-BDS was
                     more efficacious than THC-P, whereas, conversely, 
CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed
                     all combinations to be hyperadditive [T98G 48-hour 
combination index (CI) at FU50, 0.77–1.09]. Similarly, 
pretreating cells with THC-P and CBD-P together for 4 hours before 
irradiation increased their radiosensitivity
                     when compared with pretreating with either of the 
cannabinoids individually. The increase in radiosensitivity was 
associated
                     with an increase in markers of autophagy and 
apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when
                     both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm3 vs. 48.7 ± 24.9 mm3 in the control group; P
 < 0.01). Taken together, our data highlight the possibility that 
these cannabinoids can prime glioma cells to respond better
                     to ionizing radiation, and suggest a potential 
clinical benefit for glioma patients by using these two treatment 
modalities.
                     Mol Cancer Ther; 1–13. ©2014 AACR.
                  
- Received May 12, 2014.
 - Revision received September 8, 2014.
 - Accepted September 23, 2014.
 
- ©2014 American Association for Cancer Research.
 
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