HIF-1α inhibition as a novel mechanism of cardiac glycosides in cancer therapeutics
Expert Opinion on Investigational Drugs
Cardiac glycosides; Digoxin; HIF-1 inhibition
Background: Hypoxia inducible factor 1 (HIF-1α) is a potential valid cancer drug target in humans. Objectives: To search and identify novel inhibitors of HIF-1 from 'old' drugs that were already in clinical use or under clinical trial with known pharmacokinetics. Methods/results: Cell-based screen for inhibitors of HIF-1 transcriptional activity from the Hopkins Drug Library. Cardiac glycosides were the group of drugs showing significant inhibition of HIF-1 synthesis and expression of HIF-1 target genes in cancer cells. In vivo digoxin showed its antitumor activity in tumor xenografts model. Conclusions: HIF-1 is a critical target of digoxin and other cardiac glycosides for their anticancer activity. © 2009 Informa UK Ltd. All rights reserved.
Lin, J., & Carducci, M. (2009). HIF-1α inhibition as a novel mechanism of cardiac glycosides in cancer therapeutics. Expert Opinion on Investigational Drugs, 18 (2). http://dx.doi.org/10.1517/13543780802683081