title: Increased immunogenicity of colon cancer cells by selective depletion of cytochrome C.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U517, Faculty of Medicine, Dijon, France. cgarrido@u-bourgogne.fr
authors.forename: Elise
authors.initials: E
authors.lastname: Schmitt
authors.forename: Arnaud
authors.initials: A
authors.lastname: Parcellier
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Noelia
authors.initials: N
authors.lastname: Casares
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gurbuxani
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hamai
authors.forename: Marie
authors.initials: M
authors.lastname: Pequignot
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.forename: Monique
authors.initials: M
authors.lastname: Moutet
authors.forename: Annie
authors.initials: A
authors.lastname: Fromentin
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045304:Cytochromes c / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D016373:DNA, Antisense / Q000235:genetics; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection
chemical_list: D016373:DNA, Antisense; D005047:Etoposide; D004317:Doxorubicin; D045304:Cytochromes c; D019311:Staurosporine; D002945:Cisplatin