title: Evaluating the cancer therapeutic potential of cardiac glycosides.
abstract: Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na(+)/K(+)-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Calderón-Montaño
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Burgos-Morón
authors.affiliation: Department of Cell Biology, Faculty of Biology, University of Seville, Spain.
authors.forename: Manuel Luis
authors.initials: ML
authors.lastname: Orta
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Maldonado-Navas
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: García-Domínguez
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Lázaro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002301:Cardiac Glycosides / Q000737:chemistry / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D002301:Cardiac Glycosides