[en] Tumor hypoxia is a common characteristic of most solid tumors and is correlated with poor prognosis for
patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia selects cancer cells that
are resistant to apoptosis and allows the onset of mechanisms that promote cancer cells survival
including autophagy. Previously, we showed that human hepatoma HepG2 cells were protected under
hypoxia against the etoposide-induced apoptosis. In this study, respective putative contribution of
autophagy and BNIP3 in the protection conferred by hypoxia against the etoposide-induced apoptosis
was investigated. We report that autophagy is induced by etoposide, a process that is not affected by
hypoxic conditions. Using Atg5 siRNA, we show that etoposide-induced autophagy promotes apoptotic
cell death under normoxia but not under hypoxia. Then, we investigated whether the hypoxia-induced
protein BNIP3 could explain the different effect of autophagy on cell death under hypoxia or normoxia.
We show that the silencing of BNIP3 does not affect autophagy whatever the pO2 but participates in the
protective effect of hypoxia against etoposide-induced apoptosis. Together, these results suggest that
autophagy might be involved in etoposide-induced cell death only under normoxia and that BNIP3 is a
major effector of the protective mechanism conferred by hypoxia to protect cancer cells against
etoposide-induced apoptotic cell death.
Research center :
Unité de Recherche en Biologie Cellulaire
Disciplines :
Oncology
Author, co-author :
Cosse, Jean-Philippe ; Université de Liège - ULiège > GIGA-R : Epigénétique Cellulaire et Moléculaire
Rommelaere, Guillaume
Ninane, Noelle
Arnould, Thierry
Michiels, Carine
Language :
English
Title :
BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway
Publication date :
2010
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
80
Pages :
1160-1169
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FUNDP - Facultés Universitaires Notre-Dame de la Paix [BE]
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