Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death

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

Research output: Contribution to journalArticlepeer-review

Abstract

Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain 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 autophagymediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

Original languageEnglish
Pages (from-to)1629-1637
Number of pages9
JournalJournal of Investigative Dermatology
Volume135
Issue number6
DOIs
Publication statusPublished - Jan 1 2015

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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