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Exploiting Cannabinoid-Induced Cytotoxic Autophagy to Drive Melanoma Cell Death

Armstrong, Jane L. et al.

The journal of investigative dermatology. Volume 135:Issue 6 (2015); pp 1629-1637 -- Elsevier

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  • Title:
    Exploiting Cannabinoid-Induced Cytotoxic Autophagy to Drive Melanoma Cell Death
  • Author: Armstrong, Jane L.;
    Hill, David S.;
    McKee, Christopher S.;
    Hernandez-Tiedra, Sonia;
    Lorente, Mar;
    Lopez-Valero, Israel;
    Eleni Anagnostou, Maria;
    Babatunde, Fiyinfoluwa;
    Corazzari, Marco;
    Redfern, Christopher P.F.;
    Velasco, Guillermo;
    Lovat, Penny E.
  • Found In: The journal of investigative dermatology. Volume 135:Issue 6 (2015); pp 1629-1637
  • Journal Title: The journal of investigative dermatology
  • Subjects: Dermatology--Periodicals; Dermatology, Experimental--Periodicals; Skin--Diseases--Periodicals; Dermatology, Experimental; Periodicals; Skin--Diseases; Dermatology; Dewey: 616.5005
  • Rights: Licensed
  • Publication Details: Elsevier
  • 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 with Δ 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.
  • Identifier: System Number: ETOCvdc_100058840819.0x000001; Journal ISSN: 0022-202X; doi/10.1038/jid.2015.45
  • Publication Date: 2015
  • Physical Description: Electronic
  • Shelfmark(s): 5008.000000
  • UIN: ETOCvdc_100058840819.0x000001

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