UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.

Abstract

Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell death. Subsequently, we have investigated the molecular mechanisms leading to apoptosis activation. Our results show that UNBS1450 inhibits NF-κB transactivation and triggers apoptosis by cleavage of pro-caspases 8, 9 and 3/7, by decreasing expression of anti-apoptotic Mcl-1 and by recruitment of pro-apoptotic Bak and Bax protein eventually resulting in cell death.

• Authors: Tom Juncker, Claudia Cerella, Marie-Hélène Teiten, Franck Morceau, Marc Schumacher, Jenny Ghelfi, François Gaascht, Michael Schnekenburger, Estelle Henry, Mario Dicato, Marc Diederich
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 81 Issue 1 Pg. 13-23 (Jan 01 2011) ISSN: 1873-2968 [Electronic] England
• PMID: 20849830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Cardenolides
• Neoplasm Proteins
• UNBS 1450

Topics

• Apoptosis (drug effects)
• Cardenolides (chemistry, pharmacology)
• Cell Line
• Gene Expression Regulation, Neoplastic
• Humans
• Leukemia (drug therapy)
• Molecular Structure
• Neoplasm Proteins (genetics, metabolism)