Date Published: December 16, 2009
Publisher: Public Library of Science
Author(s): Andrea Perne, Markus K. Muellner, Magdalena Steinrueck, Nils Craig-Mueller, Julia Mayerhofer, Ilse Schwarzinger, Mathew Sloane, Iris Z. Uras, Gregor Hoermann, Sebastian M. B. Nijman, Matthias Mayerhofer, Alfred Lewin. http://doi.org/10.1371/journal.pone.0008292
Abstract: 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.
Partial Text: The positive inotropic effects of Digitalis purpurea extracts were first recognized over two centuries ago and digitalis-like compounds (also called cardiac glycosides (CGs) or cardiotonic steroids) are still widely used in the treatment of chronic heart failure . Since the mid 1960s numerous papers have proposed putative anti-cancer effects of CGs , , , . CGs show in vitro activity against a broad range of cell types and a number of compound screens have recently rediscovered that CGs inhibit proliferation in various assays , , , . A putative anti-cancer activity for CGs is supported by several case-control and cohort studies that loosely correlated CG treatment with lower cancer recurrence or incidence , , , , . Furthermore, using mouse models, CGs were shown to inhibit skin carcinogenesis and reduce xenograft tumor load , , , , . Particularly the strong effects in xenograft mouse models have provided a basis for the current clinical testing of these drugs and their derivatives (ClinicalTrials.gov id. NCT00281021, NCT00650910 NCT00017446, http://www.unibioscreen.com/news).
Our findings challenge the view that CGs or other Na+/K+-ATPase inhibitors hold promise as anti-cancer drugs and therefore have immediate consequences for the clinical evaluation of CGs as anti-neoplastic agents. There are at least four ongoing clinical trials in the United States and Europe testing the effect of CGs and a CG-derivative in cancer (ClinicalTrials.gov id. NCT00281021, NCT00650910 NCT00017446, http://www.unibioscreen.com/news).