Induction of apoptosis in two mammalian cell lines results in increased levels of fructose-1,6-bisphosphate and CDP-choline as determined by 31P MRS.
Programmed cell death or apoptosis was induced in human promyelocytic leukemia (HL-60) and Chinese hamster ovary (CHO-K1) cells using several cytotoxic drugs that have different modes of action, including camptothecin, ceramide, chelerythrine, etoposide, farnesol, geranyl geraniol, and hexadecylphosphocholine. The consequent changes in cellular metabolism were monitored using 31P MRS measurements on intact cells and cell extracts. Cells undergoing programmed cell death exhibited characteristic changes in the levels of glycolytic and phospholipid metabolites. The most significant changes were increases in the concentration of the glycolytic intermediate, fructose-1,6-bisphosphate and in the concentration of CDP-choline, which is an intermediate in phosphatidylcholine biosynthesis. In HL-60 cells, the increase in fructose-1,6-bisphosphate levels could be explained by depletion of cellular NAD(H) levels. All of the agents used to induce apoptosis caused the accumulation of CDP-choline. Since the resonances of this compound occur in a relatively well resolved region of tissue spectra, it could provide a marker for apoptosis that would allow the noninvasive detection of the process in vivo using 31P MRS measurements.
Williams
S N
SN
Department of Biochemistry, University of Cambridge, United Kingdom.
Anthony
M L
ML
Brindle
K M
KM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D003566:Cytidine Diphosphate Choline / Q000378:metabolism*; D005635:Fructosediphosphates / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D005635:Fructosediphosphates; D003566:Cytidine Diphosphate Choline; C029063:fructose-1,6-diphosphate