Bak and Mcl-1 are essential for Temozolomide induced cell death in human glioma.

作者: Catherine Gratas , Quentin Séry , Marion Rabé , Lisa Oliver , François M. Vallette

DOI: 10.18632/ONCOTARGET.1642

关键词: ApoptosisRNA interferenceProgrammed cell deathAutophagyBcl-2 familyBiologyTemozolomideGliomaCancer researchCell culture

摘要: // Catherine Gratas 1,2,3 , Quentin Sery 1,2,4 Marion Rabe 1,2 Lisa Oliver and Francois M. Vallette 1. Centre de Recherche en Cancerologie Nantes Angers, UMR INSERM 892 / CNRS 6299 2. Universite Nantes, F-44000, France 3. CHU F-44805, France. 4. Institut l’Ouest-Centre Rene Gauducheau, St Herblain Correspondence: Vallette, email: Keywords : temozolomide, glioma, apoptosis Bcl-2 family Received November 29, 2013 Accepted January 1, 2014 Published Abstract Temozolomide (TMZ) is an alkylating agent used for the treatment of glioblastoma multiforme (GBM), main form human brain tumours in adults. It has been reported that TMZ induced DNA lesions subsequently trigger cell death but actual mechanisms involved process are still unclear. We investigated implication major proteins TMZ-induced GBM lines at concentrations closed to reached brain during treatments. did not observe modulation autophagy these we found an induction apoptosis. Using RNA interference, showed that TMZ dependent on pro-apoptotic protein Bak but independent of protein Bax. Apoptosis was enhanced by ABT-737, inhibitor Bcl-2/Bcl-Xl/Bcl-W Mcl-1. The knock-down Mcl-1 expression increased Our results identify a Mcl-1/Bak axis thus unravel target overcome therapeutic resistance toward TMZ.

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