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In vitro effect of extracellular AMP on MCF‐7 breast cancer cells: Inhibition of glycolysis and cell proliferation
Author(s) -
Hugo Ferdinand,
Mazurek Sybille,
Zander Ute,
Eigenbrodt Erich
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041530315
Subject(s) - glycolysis , glutaminolysis , glutamine , biochemistry , cell growth , lactate dehydrogenase , biology , extracellular , intracellular , nad+ kinase , catabolism , metabolism , adenosine , fructose , carbohydrate metabolism , enzyme , amino acid
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.