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.
