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

doi:10.1016/j.bcp.2010.08.025

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

72 Citations (Scopus)

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.

Original language	English
Pages (from-to)	13-23
Number of pages	11
Journal	Biochemical Pharmacology
Volume	81
Issue number	1
DOIs	https://doi.org/10.1016/j.bcp.2010.08.025
Publication status	Published - 1 Jan 2011
Externally published	Yes

Keywords

Apoptosis
Cancer
Cardenolide
NF-κB
UNBS1450

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10.1016/j.bcp.2010.08.025

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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.",

keywords = "Apoptosis, Cancer, Cardenolide, NF-κB, UNBS1450",

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doi = "10.1016/j.bcp.2010.08.025",

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T1 - UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells

AU - Juncker, Tom

AU - Cerella, Claudia

AU - Teiten, Marie Hélène

AU - Morceau, Franck

AU - Schumacher, Marc

AU - Ghelfi, Jenny

AU - Gaascht, François

AU - Schnekenburger, Michael

AU - Henry, Estelle

AU - Dicato, Mario

AU - Diederich, Marc

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cancer

KW - Cardenolide

KW - NF-κB

KW - UNBS1450

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

Abstract

Keywords

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