Document Detail


Cardiac glycosides exert anticancer effects by inducing immunogenic cell death.
MedLine Citation:
PMID:  22814852     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient's dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell death, an effect that was associated with the inhibition of the plasma membrane Na(+)- and K(+)-dependent adenosine triphosphatase (Na(+)/K(+)-ATPase). CGs exacerbated the antineoplastic effects of DNA-damaging agents in immunocompetent but not immunodeficient mice. Moreover, cancer cells succumbing to a combination of chemotherapy plus CGs could vaccinate syngeneic mice against a subsequent challenge with living cells of the same type. Finally, retrospective clinical analyses revealed that the administration of the CG digoxin during chemotherapy had a positive impact on overall survival in cohorts of breast, colorectal, head and neck, and hepatocellular carcinoma patients, especially when they were treated with agents other than anthracyclines and oxaliplatin.
Authors:
Laurie Menger; Erika Vacchelli; Sandy Adjemian; Isabelle Martins; Yuting Ma; Shensi Shen; Takahiro Yamazaki; Abdul Qader Sukkurwala; Mickaël Michaud; Grégoire Mignot; Frederic Schlemmer; Eric Sulpice; Clara Locher; Xavier Gidrol; François Ghiringhelli; Nazanine Modjtahedi; Lorenzo Galluzzi; Fabrice André; Laurence Zitvogel; Oliver Kepp; Guido Kroemer
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143ra99     Citation Subset:  IM    
Affiliation:
INSERM, U848, F-94805 Villejuif, France.
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