Antizyme-Dependent and -Independent Mechanisms Are Responsible for Increased Spermidine Transport in Amino Acid-Restricted Human Cancer Cells

Amino acid deprivation can inhibit tumour cell proliferation. Since polyamines are required for cell growth, we hypothesised that their regulatory pathways can respond to amino acid restriction. We report here that exposure of human colon adenocarcinoma Caco-2 cells to a medium restricted for a sing...

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Published inBiochemical and biophysical research communications Vol. 256; no. 3; pp. 646 - 651
Main Authors Aubel, C., Chabanon, H., Persson, L., Thiman, L., Ferrara, M., Brachet, P.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 24.03.1999
Elsevier
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Summary:Amino acid deprivation can inhibit tumour cell proliferation. Since polyamines are required for cell growth, we hypothesised that their regulatory pathways can respond to amino acid restriction. We report here that exposure of human colon adenocarcinoma Caco-2 cells to a medium restricted for a single amino acid, but not for D-glucose, activates spermidine transport. The increase was rapid and seemed transient with a maximum 4-6 hr after amino acid removal. Kinetics showed that the maximal velocity of transport was solely increased in L-methionine- or L-leucine-deprived cells, indicating increased number of transporters. The intracellular level of complex of ornithine decarboxylase (ODC) with antizyme, a negative regulator of polyamine transport, was decreased by 16-29% in amino acid-deprived cells. However, exposure to limited amounts of amino acid increased transport without altering the ODC-antizyme complex level. We propose that antizyme-independent mechanisms, sensitive to the amino acid concentration, also participate to the control of spermidine transport.
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ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.0397