Cancer cell death by programmed necrosis?
A recent paper by Zong et al. 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.
Borst
Piet
P
Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
Rottenberg
Sven
S
D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D006019:Glycolysis; D006801:Humans; D009243:NAD / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D009243:NAD