HIF-1α inhibition as a novel mechanism of cardiac glycosides in cancer therapeutics

Abstract

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.

Keywords::

• cardiac glycosides
• digoxin
• HIF-1 inhibition