1. ¹INSERM U 601-Equipe 4, 9 Quai MONCOUSU, Cedex 01, Nantes, France
2. ²Faculty of Medicine, University of Nantes, 9 quai MONCOUSU, Cedex 01, Nantes, France
3. ³Department of Anatomo-Pathology, G&R Laennec Hospital, CHU, Nantes, France
4. ⁴Department of Neurosurgery, G&R Laennec Hospital, CHU, Nantes, France

Correspondence: Dr FM Vallette, INSERM U601, 9 Quai MONCOUSU 44035 Nantes, Cedex 01, France. E-mail: francois.vallette@univ-nantes.fr

Received 23 August 2006; Revised 7 December 2006; Accepted 11 December 2006; Published online 19 March 2007.

Abstract

Prostaglandin E₂ plays multiple roles both in the physiology and the physiopathology of human brain, which are not completely understood. We have identified in a subset of human glioblastoma multiforme (GBM) tumors, the most common form of adult brain cancer, an increased expression of mPGES-1, the enzyme which catalyses the isomerization of PGH₂ into PGE₂ downstream of cyclooxygenase 2 (COX-2). The sensitivity of primary cultures of GBM to apoptosis was augmented by the overexpression of mPGES-1, whereas the knockdown of its expression by shRNA decreased the apoptotic threshold in vitro and stimulated tumor growth in vivo. Adding extracellular PGE₂ in the culture medium failed to reproduce mPGES-1 effect on the cell viability in vitro. However, the intracellular injection of PGE₂ induced a dose-dependent apoptosis in GBM cultures, which was dependent on the presence of Bax, a pro-apoptotic protein. We show that PGE₂ physically associates with Bax, triggering its apoptotic-like change in conformation and its subsequent association with mitochondria. Our results raise questions about the role of PGE₂ in the control of apoptosis and in its potential impact in central nervous system pathologies.