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

Authors

Jianqing Lin, The Sidney Kimmel Comprehensive Cancer Center
Michael A. Carducci, The Sidney Kimmel Comprehensive Cancer Center

Document Type

Journal Article

Publication Date

2-1-2009

Journal

Expert Opinion on Investigational Drugs

Volume

18

Issue

2

DOI

10.1517/13543780802683081

Keywords

Cardiac glycosides; Digoxin; HIF-1 inhibition

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. © 2009 Informa UK Ltd. All rights reserved.

APA Citation

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