ORBi: Piret Jean-Pascal - Hypoxia protects HepG2 cells against etoposide-induced apoptosis VIA a HIF-1-independent pathway

Reference : Hypoxia protects HepG2 cells against etoposide-induced apoptosis VIA a HIF-1-independent...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/2268/84917

Title :	Hypoxia protects HepG2 cells against etoposide-induced apoptosis VIA a HIF-1-independent pathway
Language :	English
Author, co-author :	Piret, Jean-Pascal [> >]
	Cosse, Jean-Philippe [Université de Liège - ULg > > GIGA-R : Epigénétique Cellulaire et Moléculaire >]
	Ninane, Noelle [> >]
	Raes, Martine [> >]
	Michiels, Carine [> >]
Publication date :	2006
Journal title :	Experimental Cell Research
Volume :	312
Pages :	2908-2920
Audience :	International
ISSN :	0014-4827
Keywords :	[en] Hypoxia ; HIF-1 ; AP-1 ; Apoptosis ; Etoposide
Abstract :	[en] Tumor hypoxia has been described to increase the resistance of cancer cells to radiation therapy and chemotherapy. It also supports the invasiveness and metastatic potential of the tumor. However, few data are available on the transduction pathway set up under hypoxia and leading to this resistance against anti-cancer therapies. HIF-1, the main transcription factor activated by hypoxia, has been recently shown to participate to this process although its role as an anti- or a pro-apoptotic protein is still controversy. In this study, we showed that hypoxia protected HepG2 cells against etoposide-induced apoptosis. The effect of hypoxia on cell death was assayed by measuring different parameters of the apoptotic pathway, like DNA fragmentation, caspase activity and PARP-1 cleavage. The possible implication of HIF-1 in the anti-apoptotic role of hypoxia was investigated using HIF-1α siRNA. Our results indicated that HIF-1 is not involved in the hypoxia-induced antiapoptotic pathway. Another transcription factor, AP-1, was studied for its potential role in the hypoxia-induced protection against apoptosis. Specific inhibition of AP-1 decreased the protection effect of hypoxia against etoposide-induced apoptosis. Together, all these data underline that hypoxia could mediate its anti-apoptotic role via different transcription factors depending on the cellular context and pro-apoptotic stimuli.
Research units :	Unité de Recherche en Biologie Cellulaire
Funders :	Facultés Universitaires Notre-Dame de La Paix
Target :	Researchers
Permalink :	http://hdl.handle.net/2268/84917
DOI :	10.1016/j.yexcr.2006.05.018

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