Pubblicazioni

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

Autori:
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
Titolo:
Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism
Anno:
2011
Tipologia prodotto:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Nazioni degli autori:
ITALIA
Lingua:
Inglese
Formato:
Elettronico
Referee:
No
Nome rivista:
CELL DEATH & DISEASE
ISSN Rivista:
2041-4889
N° Volume:
2
Intervallo pagine:
e152-e152
Codice PMID:
21525939
Parole chiave:
pancreatic cancer, reactive oxygen species, gemcitabine, cannabinoid, ER stress, autophagy
Breve descrizione dei contenuti:
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.
Pagina Web:
http://preview.ncbi.nlm.nih.gov/pubmed/21525939
Id prodotto:
60428
Handle IRIS:
11562/351870
depositato il:
28 febbraio 2012
ultima modifica:
2 novembre 2016
Citazione bibliografica:
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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