Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Juncker, Tom
  • Cerella, Claudia
  • Teiten, Marie-Hélène
  • Morceau, Franck
  • Schumacher, Marc
  • Ghelfi, Jenny
  • Gaascht, François
  • Schnekenburger, Michael
  • Henry, Estelle
  • Dicato, Mario
  • Diederich, Marc
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 2010
Accepted Date
Aug 27, 2010
Volume
81
Issue
1
Pages
13–23
Identifiers
DOI: 10.1016/j.bcp.2010.08.025
Source
Elsevier
Keywords
License
Unknown

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.

Report this publication

Statistics

Seen <100 times