Hypoxia protects HepG2 cells against etoposide-induced apoptosis VIA a HIF-1-independent pathway

J.-P. Piret, J.-P. Cosse, N. Ninane, M. Raes, C. Michiels

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs


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 anti-apoptotic 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.
langue originaleAnglais
Pages (de - à)2908-2920
Nombre de pages13
journalExperimental Cell Research
Numéro de publication15
Les DOIs
Etat de la publicationPublié - 2006

Empreinte digitale

Examiner les sujets de recherche de « Hypoxia protects HepG2 cells against etoposide-induced apoptosis VIA a HIF-1-independent pathway ». Ensemble, ils forment une empreinte digitale unique.

Contient cette citation