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

Tom Juncker, Claudia Cerella, Marie Hélène Teiten, Franck Morceau, Marc Schumacher, Jenny Ghelfi, François Gaascht, Michael Schnekenburger, Estelle Henry, Mario Dicato, Marc Diederich

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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-??B 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. ?? 2010 Elsevier Inc.
Original languageEnglish (US)
Pages (from-to)13-23
Number of pages11
JournalBiochemical Pharmacology
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • Apoptosis
  • Cancer
  • Cardenolide
  • NF-??B
  • UNBS1450

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