BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway

[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/Unit :

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 :

Pages :

1160-1169

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

FUNDP - Facultés Universitaires Notre-Dame de la Paix

Available on ORBi :

since 15 February 2011

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