title: Cardiac glycosides in cancer therapy: from preclinical investigations towards clinical trials.
abstract: Cardiac glycosides have a long history in the treatment of cardiac disease. However, several preclinical studies as well as two phase I studies have shown that cardenolides may also possess anticancer effects. The mechanisms of these anticancer effects may include intracellular decrease of K(+) and increase of Na(+) and Ca(2+); intracellular acidification; inhibition of IL-8 production and of the TNF-α/NF-κB pathway; inhibition of DNA topoisomerase II and activation of the Src kinase pathway. To date three cardiac glycosides have been developed for treatment of cancer and were tested in a phase 1 clinical trial to determine dose limiting toxicities and maximum tolerated dose. Future studies of this novel class of anticancer drugs are warranted to determine their possible role in cancer treatment.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. M.Slingerland@lumc.nl
authors.forename: M
authors.initials: M
authors.lastname: Slingerland
authors.forename: C
authors.initials: C
authors.lastname: Cerella
authors.forename: H J
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: M
authors.initials: M
authors.lastname: Diederich
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002301:Cardiac Glycosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D002301:Cardiac Glycosides