TY - JOUR
T1 - Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death
AU - Armstrong, Jane L.
AU - Hill, David S.
AU - McKee, Christopher S.
AU - Hernandez-Tiedra, Sonia
AU - Lorente, Mar
AU - Lopez-Valero, Israel
AU - Anagnostou, Maria Eleni
AU - Babatunde, Fiyinfoluwa
AU - Corazzari, Marco
AU - Redfern, Christopher P F
AU - Velasco, Guillermo
AU - Lovat, Penny E.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2015.45
DO - 10.1038/jid.2015.45
M3 - Article
C2 - 25674907
AN - SCOPUS:84938096558
VL - 135
SP - 1629
EP - 1637
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -