Journal
DRUG RESISTANCE UPDATES
Volume 7, Issue 6, Pages 321-324Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2004.11.003
Keywords
alkylating agents; apoptosis; glycolysis; NAD(+); NADP(+); necrosis; PARP
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A recent paper by Zong et al. [2004. Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 18, 1272-12821 describes how alkylating agents kill cells by a process they term programmed necrosis, induced by excessive activation of PARP resulting in degradation of cytosolic NAD(+) and inhibition of glycolysis. We argue that it is not obvious whether chemotherapy in patients can induce sufficient NAD(+) loss to affect glycolysis; that the programmed nature of the necrosis requires more evidence; and that there are mechanisms making cancer cells hypersensitive to DNA damage other than their high rate of aerobic glycolysis. (c) 2004 Elsevier Ltd. All rights reserved.
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