Research ArticleCancer

Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death

Science Translational Medicine  18 Jul 2012:
Vol. 4, Issue 143, pp. 143ra99
DOI: 10.1126/scitranslmed.3003807

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A Cancer Double Feature—3807

A traditional chemotherapeutic drug performs a one-act play: It enters and kills a dividing cancer cell and then takes its bow. However, some chemotherapeutics have a wider range—they not only kill individual cancer cells but also do so in such a way that the dead cells function as a vaccine that primes the immune system to attack other cancer cells. Menger et al. now identify cardiac glycosides as potent inducers of this so-called immunogenic cell death.

Using fluorescence microscopy to detect the hallmarks of immunogenic cell death, the authors identified cardiac glycosides, such as the heart drug digoxin, as immunogenic cell death inducers. They then verified that these drugs had anticancer effects in mice with intact immune systems but not in mice that lacked functional immunity. Cancer cells that died from digoxin exposure then effectively functioned as a vaccine—stimulating the immune system so that growth of future cancers is prevented. Indeed, human cancer patients on chemotherapy who happened to be taking the cardiac glycoside digoxin to treat other medical conditions had improved overall survival compared with patients who were not taking these drugs. Although efficacy in cancer patients remains to be formally tested, cardiac glycosides may augment chemotherapeutic response—forcing cancer to bow out.