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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-4465

Rieger, J; Lemke, D; Maurer, G; Weiler, M; Frank, B; Tabatabai, G; Weller, M; Wick, W (2008). Enzastaurin-induced apoptosis in glioma cells is caspase-dependent and inhibited by BCL-XL. Journal of Neurochemistry, 106(6):2436-2448.

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Abstract

The novel protein kinase C-beta inhibitor enzastaurin (ENZA) induced apoptosis in LNT-229 and T98G cells whereas A172 cells were resistant. Further, ENZA reduced proliferation in glioblastoma-initiating cells T 269 and T 323 but did not induce apoptosis. ENZA-induced apoptosis involved cleavage of caspases 3, 8, and 9 and led to mitochondrial cytochrome c release and was strongly suppressed by the broad spectrum caspase inhibitor zVAD-fmk but only slightly by the expression of the viral caspase 1/8 inhibitor cytokine response modifier-A. ENZA did not reduce the phosphorylation of protein kinase B (Akt), but of p70 S6 kinase and of its substrate S6 protein in T98G cells. Inhibition of the phosphatidylinositol 3 kinase signaling pathway did not restore sensitivity of A172 cells towards ENZA, and constitutively active Akt did not protect LNT-229 and T98G cells from ENZA-induced apoptosis. Dephosphorylation of glycogen synthase kinase 3beta, a biomarker of ENZA action, and cell death induction by ENZA were separately regulated. Inhibition or activation of Akt only weakly modulated ENZA-induced dephosphorylation of glycogen synthase kinase 3beta. In ENZA-resistant A172 cells, apoptosis ligand 2 (Apo2L.0)-induced cleavage of caspases 3, 8, and 9 was increased by ENZA, resulting in synergistic activity of ENZA and Apo2L.0.

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19 citations in Web of Science®
17 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:September 2008
Deposited On:31 Oct 2008 12:13
Last Modified:28 Nov 2013 01:36
Publisher:Wiley-Blackwell
ISSN:0022-3042
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1111/j.1471-4159.2008.05586.x
PubMed ID:18662322

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