Fiche publication
Date publication
avril 2004
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen
,
Pr GHIRINGHELLI François
Tous les auteurs :
Schmitt E, Parcellier A, Ghiringhelli F, Casares N, Gurbuxani S, Droin N, Hamai A, Pequignot M, Hammann A, Moutet M, Fromentin A, Kroemer G, Solary E, Garrido C
Lien Pubmed
Résumé
We and others have previously reported in an in vivo rat colon cancer cell model that cell death precedes and is necessary for the development of a specific antitumoral immune response. To sensitize colon cancer cells to death, we depleted cytochrome c by stable transfection with an antisense construct. Cytochrome c depletion sensitizes human and rat colon cancer cells to a nonapoptotic, nonautophagic death induced by various stimuli. This increased sensitization to a necrosis-like cell death may be related to a decrease in cellular ATP levels and an increase in reactive oxygen species production caused by cytochrome c depletion. In vivo, depletion of cytochrome c decreases the tumorigenicity of colon cancer cells in syngeneic rats without influencing their growth in immune-deficient animals. Furthermore, decreased expression of cytochrome c in tumor cells facilitates in vivo "necrotic" cell death and the induction of a specific immune response. These results delineate a novel strategy to sensitize colon cancer cells to chemotherapy and to increase their immunogenicity in immuno-competent hosts.
Mots clés
Animals, Apoptosis, drug effects, Cisplatin, pharmacology, Colonic Neoplasms, drug therapy, Cytochromes c, biosynthesis, DNA, Antisense, genetics, Down-Regulation, Doxorubicin, pharmacology, Etoposide, pharmacology, HCT116 Cells, HT29 Cells, Humans, Macrophages, immunology, Mice, Rats, Staurosporine, pharmacology, Transfection
Référence
Cancer Res.. 2004 Apr;64(8):2705-11
