Cardiac glycosides induce cell death in human cells by inhibiting general protein synthesis.

ABSTRACT:

Background

Cardiac glycosides are Na(+)/K(+)-pump inhibitors widely used to treat heart failure. They are also highly cytotoxic, and studies have suggested specific anti-tumor activity leading to current clinical trials in cancer patients. However, a definitive demonstration of this putative anti-cancer activity and the underlying molecular mechanism has remained elusive.

Methodology/principal findings

Using an unbiased transcriptomics approach, we found that cardiac glycosides inhibit general protein synthesis. Protein synthesis inhibition and cytotoxicity were not specific for cancer cells as they were observed in both primary and cancer cell lines. These effects were dependent on the Na(+)/K(+)-pump as they were rescued by expression of a cardiac glycoside-resistant Na(+)

SUBMITTER: Perne A 

PROVIDER: S-EPMC2788214 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature