Thymidylate synthase inhibition triggers glucose-dependent apoptosis in p53-negative leukemic cells

FEBS Letters
C Muñoz-PinedoA López-Rivas

Abstract

Chemotherapeutic drugs that inhibit the synthesis of DNA precursor thymidine triphosphate cause apoptosis, although the mechanism underlying this process remains rather unknown. Here, we describe thymineless death of human myeloid leukemia U937 cells treated with the thymidylate-synthase inhibitor 5'-fluoro- 2'-deoxyuridine (FUdR). This apoptotic process was shown to be independent of p53, reactive oxygen species generation and CD95 activation. Caspases were activated downstream of cytochrome c but upstream of mitochondrial depolarization. Furthermore, FUdR-induced apoptosis required the presence of glucose in the culture medium at a step upstream of the release of cytochrome c from mitochondria.

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Citations

Mar 6, 2010·Cell Death and Differentiation·A Caro-MaldonadoC Muñoz-Pinedo
Sep 25, 2010·Nucleic Acids Research·András Horváth, Beáta G Vértessy
Apr 6, 2005·Biomedical Research·Masahiko OhataMamoru Isemura
Nov 23, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S GiudiceC Magnoni
Oct 26, 2010·Oncogene·N El MjiyadC Muñoz-Pinedo

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