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Lookup NU author(s): Dr Jane Renwick, Dr David Hill, Christopher McKee, Maria Anagnostou, Fiyinfoluwa Babatunde, Dr Chris RedfernORCiD, Professor Penny Lovat
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain o10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wild-type tumors. Targeting autophagy is a means to promote cancer cell death in chemotherapy-resistant tumors, and the aim of this study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma. Treatment with Δ9-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagymediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.
Author(s): Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I, Anagnostou ME, Babatunde F, Corazzari M, Redfern CPF, Velasco V, Lovat PE
Publication type: Article
Publication status: Published
Journal: Journal of Investigative Dermatology
Year: 2015
Volume: 135
Issue: 6
Pages: 1629-1637
Print publication date: 01/06/2015
Online publication date: 10/02/2015
Acceptance date: 21/01/2014
Date deposited: 23/06/2015
ISSN (print): 0022-202X
ISSN (electronic): 1523-1747
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/jid.2015.45
DOI: 10.1038/jid.2015.45
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