[Effect of chlorine-methylated quaternary ammonium on human gastric cancer cell proliferation].
This work reports the action of some choline derivatives on the proliferation of the human gastric cancer cell line HGT-1 which does not secrete mucus or carcino-embryonic antigen, but express histamine H2 and somatostatin receptors. The structural family of the tested molecules (GMS-003F, GMS-005F et GMS-010F) belongs to the chloruro-methylated quaternary ammonium. A dose-dependent growth inhibitory effect, significant but weak (20%), was observed at 1-10 mM concentrations of GMS-003F, GMS-005F and choline. GMS-010F was more potent than the other derivatives to inhibit the growth of the cell line (IC50: 1 microM and total inhibition at 10 microM). Moreover, these compounds exert an effect on the membrane potential of this cell line, as measured by the capacity of membrane to concentrate fluorescent dyes (carbocyanines) in response to a membrane potential variation following the addition of a K+ ionophore, valinomycine: 10 mM GMS-005F or choline significantly reduced the fluorescence signal as compared to untreated cells. With GMS-010F, this effect was significant at concentrations as low as 0.1 microM and maximal at 1 microM. These results seem to indicate that the chemical series of the GMS-010F presents a potent growth inhibitory activity of a highly tumorigenic gastric cancer cell line. The presence of a quaternary ammonium group, responsible for some alkylating effect, could explain such a result.
Rémy-Heintz
N
N
INSERM CJF 92-07, Université de Montpellier, Faculté de Pharmacie, France.
Bali
J P
JP
Sénelar
R
R
Gastaud
J M
JM
D000230:Adenocarcinoma / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002713:Chlorine / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008745:Methylation; D008875:Middle Aged; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology* / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000644:Quaternary Ammonium Compounds; D002713:Chlorine; D002794:Choline
Effet sur la prolifération de cellules tumorales gastriques de sels d'ammonium quaternaires chlorurométhylés.