UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.
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.
Juncker
Tom
T
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540 Luxembourg, Luxembourg.
Cerella
Claudia
C
Teiten
Marie-Hélène
MH
Morceau
Franck
F
Schumacher
Marc
M
Ghelfi
Jenny
J
Gaascht
François
F
Schnekenburger
Michael
M
Henry
Estelle
E
Dicato
Mario
M
Diederich
Marc
M
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
D002298:Cardenolides; D009363:Neoplasm Proteins; C510008:UNBS 1450