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

Biotechnology Institute

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

72 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 language	English (US)
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
State	Published - Jan 1 2011

Keywords

Apoptosis
Cancer
Cardenolide
NF-??B
UNBS1450

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bcp.2010.08.025

http://www.mendeley.com/research/unbs1450-steroid-cardiac-glycoside-inducing-apoptotic-cell-death-human-leukemia-cells

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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-??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.",

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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-??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.

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-??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.

KW - Apoptosis

KW - Cancer

KW - Cardenolide

KW - NF-??B

KW - UNBS1450

U2 - 10.1016/j.bcp.2010.08.025

DO - 10.1016/j.bcp.2010.08.025

M3 - Article

C2 - 20849830

SN - 0006-2952

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EP - 23

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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