Document Detail

Cardiac glycosides exert anticancer effects by inducing immunogenic cell death.
MedLine Citation:
PMID:  22814852     Owner:  NLM     Status:  In-Data-Review    
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.
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    
INSERM, U848, F-94805 Villejuif, France.
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