Publications

Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism  (2011)

Authors:
Donadelli M; Dando I; Zaniboni T; Costanzo C; Dalla Pozza E; Scupoli MT; Scarpa A; Zappavigna S; Marra M; Abbruzzese A; Bifulco M; Caraglia M; Palmieri M
Title:
Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism
Year:
2011
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Nations of authors:
ITALIA
Language:
Inglese
Format:
Elettronico
Referee:
No
Name of journal:
CELL DEATH & DISEASE
ISSN of journal:
2041-4889
N° Volume:
2
Page numbers:
e152-e152
Code PMID:
21525939
Keyword:
pancreatic cancer, reactive oxygen species, gemcitabine, cannabinoid, ER stress, autophagy
Short description of contents:
Gemcitabine (GEM, 2',2'-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of < 20%. The purpose of our work was to improve GEM activity by addition of cannabinoids. Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-ºB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments. The antiproliferative synergism is prevented by the radical scavenger N-acetyl-L-cysteine and by the specific NF-ºB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-ºB by GEM is required for this effect. In addition, we report that neither apoptotic nor cytostatic mechanisms are responsible for the synergistic cell growth inhibition, which is strictly associated with the enhancement of endoplasmic reticulum stress and autophagic cell death. Noteworthy, the antiproliferative synergism is stronger in GEM-resistant pancreatic cancer cell lines compared with GEM-sensitive pancreatic cancer cell lines. The combined treatment strongly inhibits growth of human pancreatic tumor cells xenografted in nude mice without apparent toxic effects. These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells.
Web page:
http://preview.ncbi.nlm.nih.gov/pubmed/21525939
Product ID:
60428
Handle IRIS:
11562/351870
Deposited On:
February 28, 2012
Last Modified:
November 2, 2016
Bibliographic citation:
Donadelli M; Dando I; Zaniboni T; Costanzo C; Dalla Pozza E; Scupoli MT; Scarpa A; Zappavigna S; Marra M; Abbruzzese A; Bifulco M; Caraglia M; Palmieri M, Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism «CELL DEATH & DISEASE» , vol. 22011pp. e152-e152

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