Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells

0346305 - ÚOCHB 2011 RIV GR eng J - Journal Article
Mertlíková-Kaiserová, Helena - Votruba, Ivan - Matoušová, Marika - Holý, Antonín - Hájek, Miroslav
Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells.
Anticancer Research. Roč. 30, č. 7 (2010), s. 2791-2798. ISSN 0250-7005. E-ISSN 1791-7530
R&D Projects: GA MŠMT 1M0508
Institutional research plan: CEZ:AV0Z40550506
Keywords : acyclic nucleoside phosphonate * programmed cell death * CCRF-CEM cells * cell cycle
Subject RIV: CC - Organic Chemistry
Impact factor: 1.656, year: 2010

9-[2-(phosphonomethoxy)ethyl] guanine (PMEG) is a guanine acyclic nucleotide analog whose prodrugs are being investigated for chemotherapy of lymphomas. The objective of this study was to determine the requirements for caspase and CD95/Fas activation in PMEG-induced apoptosis and the influence of PMEG on cell cycle regulatory proteins in CCRF-CEM cells. As for cell cycle regulation, cyclin E1 was found to be up-regulated following PMEG treatment. Although an increase of caspase 3, 8 and 9 proteolytic activity was observed, neither pretreatment of the cells with cell-permeable caspase inhibitors nor blocking the death receptor with anti-Fas antibody did prevent apoptosis induced by PMEG. It was concluded that PMEG-induced apoptosis is caspase- and CD95/Fas-independent.
Permanent Link: http://hdl.handle.net/11104/0187373