Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step of polyamine uptake is the binding of polyamines to the cell membrane. In order to characterize the specificity of the putrescine binding sites at the surface of the glioblastoma cells (U251), we have carried out competition experiments between putrescine bound to latex microspheres and vizualized by scanning electron microscopy and a series of N,N'-tetramethyl-alpha,omega-diaminoalkanes. N,N'-tetramethyl-1,4-butanediamine (N,N'-tetramethylputrescine) and higher homologs inhibit the latex putrescine binding to the cell surface and concomitantly cell proliferation. [14C] putrescine uptake was mainly inhibited by the lower homologs, which were devoid of antiproliferative effects. Our results suggest that putrescine uptake by the human glioblastoma cell line U251, and putrescine binding to the surface of these cells are independent processes. The potential relationship between antitumor effect of N,N'-tetramethyl-alpha,omega-diaminoalkanes and its binding to a specific putrescine acceptor site is discussed.
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PMID:Effects of a series of homologous alpha,omega-dimethylaminoalkanes on cell proliferation: binding and uptake of putrescine by a human glioblastoma cell line (U251) in culture. 210 20

In a previous study, we identified regions on the surface of tumor cells which act as acceptor sites for putrescine (Put) and studied the competition between structural analogs of Put (N,N'-tetramethyl-alpha,omega-diaminoalkanes) and Put bound to latex microspheres. A chain of four to seven carbons was necessary for inhibition of Put-latex binding to the cell surface of human glioblastoma (U251) cells. We show here that under the experimental conditions, N,N'-tetramethyl-1,4-butanediamine and N,N'-tetramethyl-1,7-heptanediamine exhibit an antitumor effect. In a first step (1-48 h after treatment), cells exposed to these compounds show large intracellular vacuoles. We failed to detect any acid phosphatase activity in these intracellular structures revealing that they were not lysosomes. Electron microscopy observations argue for the conclusion that these vacuoles are an hypertrophy of the endoplasmic reticulum (ER) and/or of the Golgi vesicles. Our hypothesis is that this typical effect of the analogs reveals that ER could be a physiological target of endogenous polyamines. At a later stage (6 days after treatment), the cells undergo morphological and biochemical changes: thin and long expansions characterize the cells and the GFA protein is overexpressed. Correlated to both these effects, karyotypic modifications are found in chromosomes 3 and 6. These changes evoke a differentiation of the treated cells. The work provides evidence that N-methylated polyamine analogs taking the place of endogenous putrescine demonstrate a hopeful antitumor effect.
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PMID:The effects of structural analogs of putrescine on proliferation, morphology and karyotype of glioblastoma cells in culture. 836 99