Pubblicazioni

Autori:

Donadelli, Massimo; Dando, Ilaria; Zaniboni, Tatyana; Costanzo, Chiara; DALLA POZZA, Elisa; Scupoli, Maria; Scarpa, Aldo; Zappavigna, S; Marra, M; Abbruzzese, A; Bifulco, M; Caraglia, M; Palmieri, Marta

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

Lingua:

Inglese

Formato:

Elettronico

Referee:

No

Nome rivista:

CELL DEATH & DISEASE

ISSN Rivista:

2041-4889

N° Volume:

2

Intervallo pagine:

e152-e152

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-κB-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-κB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-κB 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:

12 novembre 2022

Citazione bibliografica:

Donadelli, Massimo; Dando, Ilaria; Zaniboni, Tatyana; Costanzo, Chiara; DALLA POZZA, Elisa; Scupoli, Maria; Scarpa, Aldo; Zappavigna, S; Marra, M; Abbruzzese, A; Bifulco, M; Caraglia, M; Palmieri, Marta, Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism «CELL DEATH & DISEASE» , vol. 2 , 2011 , pp. e152-e152

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