title: 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.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg.
authors.forename: Tom
authors.initials: T
authors.lastname: Juncker
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Teiten
authors.forename: Franck
authors.initials: F
authors.lastname: Morceau
authors.forename: Marc
authors.initials: M
authors.lastname: Schumacher
authors.forename: Jenny
authors.initials: J
authors.lastname: Ghelfi
authors.forename: François
authors.initials: F
authors.lastname: Gaascht
authors.forename: Michael
authors.initials: M
authors.lastname: Schnekenburger
authors.forename: Estelle
authors.initials: E
authors.lastname: Henry
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002298:Cardenolides / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002298:Cardenolides; D009363:Neoplasm Proteins; C510008:UNBS 1450