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

Andrea Perne1, Markus K Muellner, Magdalena Steinrueck

  • 1Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria.

Plos One
|December 18, 2009
PubMed
Abstract

Insights

Cardiac glycosides, used for heart failure, inhibit protein synthesis and harm all cells, not just cancer cells. Their anti-cancer effects in mouse models may not translate to humans.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Cardiac glycosides are Na(+)/K(+)-pump inhibitors used clinically for heart failure.
  • These compounds exhibit cytotoxicity and have been investigated for anti-cancer properties, yet their mechanism remains unclear.

Purpose of the Study:

  • To investigate the molecular mechanism underlying the cytotoxic effects of cardiac glycosides.
  • To evaluate the specificity of cardiac glycosides against cancer cells.

Main Methods:

  • Unbiased transcriptomics analysis was employed to identify cellular responses to cardiac glycosides.
  • Experiments involved both primary and cancer cell lines, as well as investigations into Na(+)/K(+)-pump dependency and rodent cell resistance.

Main Results:

  • Cardiac glycosides were found to inhibit general protein synthesis in both cancer and non-cancerous cells.
  • Cytotoxicity was not specific to cancer cells and was dependent on the Na(+)/K(+)-pump.
  • Rodent cells demonstrated significant resistance to cardiac glycosides compared to human cells.

Conclusions:

  • The observed cytotoxicity of cardiac glycosides is attributed to the inhibition of general protein synthesis.
  • Differences in Na(+)/K(+)-pump activity and physiology between humans and rodents explain discrepancies in observed anti-tumor effects.
  • Reevaluation of mouse xenograft models for cardiac glycoside anti-cancer activity is warranted, and ongoing clinical trials in humans raise concerns.

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