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Article Publish Status: FREE
Abstract Title:

Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death.

Abstract Source:

J Invest Dermatol. 2015 Jun ;135(6):1629-37. Epub 2015 Feb 10. PMID: 25674907

Abstract Author(s):

Jane L Armstrong, David S Hill, Christopher S McKee, Sonia Hernandez-Tiedra, Mar Lorente, Israel Lopez-Valero, Maria Eleni Anagnostou, Fiyinfoluwa Babatunde, Marco Corazzari, Christopher P F Redfern, Guillermo Velasco, Penny E Lovat

Article Affiliation:

Jane L Armstrong

Abstract:

Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain<10%. 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 withΔ(9)-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 autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

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