In vitro effect of extracellular AMP on MCF-7 breast cancer cells: Inhibition of glycolysis and cell proliferation

Autor: F Hugo, Erich Eigenbrodt, Sybille Mazurek, Ute Zander
Rok vydání: 1992
Předmět:
Zdroj: Journal of Cellular Physiology. 153:539-549
ISSN: 1097-4652
0021-9541
DOI: 10.1002/jcp.1041530315
Popis: MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium. The effects on cell proliferation, glycolysis, and glutaminolysis were investigated. Of all adenosine derivatives tested, AMP was the most efficient inhibitor of cell proliferation. In AMP-treated cells, DNA synthesis decreased, whereas RNA and protein syntheses rose normally with time. In terms of carbohydrate metabolism, lactate production from glucose was drastically reduced; therefore, most of lactate produced must have been derived from glutamine. Increase in the enzyme activities involved in glutatmate degradation and in the malate-aspartate shuttle were observed. In contrast, actual glycolytic flux rates declined, whereas key glycolytic enzyme activities increased. Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells. Based on the lowered NAD level in the AMP-treated cells, lactate dehydrogenase, but not malate dehydrogenase, was impaired; thereby the whole of glycolysis was inhibited. In compensation, glutamine catabolism was increased. NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels. A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented. © 1992 Wiley-Liss, Inc.
Databáze: OpenAIRE
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