Effects of a series of homologous α,ω‐dimethylaminoalkanes on cell proliferation: binding and uptake of putrescine by a human glioblastoma cell line (U251) in culture

Abstract

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.

Long chain diamines inhibit growth of C6 glioma cells according to their hydrophobicity. An in vitro and molecular modeling study

“…Douaud et al (1997) observed cytotoxic activities of dimethylsilane polyamine analogues, suggesting that the higher lipophilicity of these drugs compared to natural polyamines allows them to bind to hydrophobic groups in the vicinity of anionic binding sites. The importance of the hydrophobic character of polyamine analogues on proliferation of U251 human glioblastoma cells was also proposed by Quemener et al (1990). They demonstrated increasing antiproliferative activity of putrescine analogues (N,N'-tetramethyl-α,ω-diaminoalkanes) with an increasing CH 2 -chain length, suggesting that the enhanced hydrophobicity is related to the growth-inhibitory effect.…”

“…An increase in hydrophobicity of polyamine analogues compared to natural polyamines has been suggested to play an important role for their antiproliferative properties (Quemener et al 1990;Douaud et al 1997).…”

Flow cytometric analysis of in vivo polyamine deprivation in Lewis lung carcinoma (3LL) cells using the monoclonal antibody SPM8‐2

“…Specific binding sites with high affinity for polyamines on cell membrane have been demonstrated using latex-bound polyamines (23,24). Whether the antibody displays such non-covalently bound polyamines or only polyamines bound to the membrane proteins as a product of a transglutaminase-catalyzed reaction is still under question.…”

The effects of structural analogs of putrescine on proliferation, morphology and karyotype of glioblastoma cells in culture

“…We were able to show that cell membranes bind putrescine (Put) bound to latex microspheres [15]. Structural analogs of putrescine, the homologous ~,w-dimetbylaminoaminoalkanes, conapete with Put-latex for the binding sites, if their carbon chain contains four to seven C-atoms [15].…”

“…We were able to show that cell membranes bind putrescine (Put) bound to latex microspheres [15]. Structural analogs of putrescine, the homologous ~,w-dimetbylaminoaminoalkanes, conapete with Put-latex for the binding sites, if their carbon chain contains four to seven C-atoms [15]. These analogs have an antiproli ferative action on the U251 cell line, whereas the lower homologue with two carbon atoms (N,N'-tetramethyl-l,2-ethanediamine) does not compete for binding, but it reduces more than the other homologues the uptake of putrescine [15] and spermidine [10].…”