EFFECT OF CHLORURO-METHYLATED QUATERNARY AMMONIUM ON HUMAN GASTRIC-CANCER CELLS PROLIFERATION

This work reports the action of some choline derivatives on the prolif eration of the human gastric cancer cell line HGT-1 which does not sec rete mucus or carcino-embryonic antigen, but express histamine H-2 and somatostatin receptors. The structural family of the tested molecules (GMS-003F, GMS-005F et GMS-010F) belongs to the chloruro-methylated q uaternary ammonium. A dose-dependent growth inhibitory effect, signifi cant but weak (20 %), was observed at 1-10 mM concentrations of GMS-00 3F, GMS-005F and choline. GMS-010F was more potent than the other deri vatives to inhibit the growth of the cell line (IC50 : 1 mu M and tota l inhibition at 10 mu M). Moreover, these compounds exert an effect on the membrane potential of this cell line, as measured by the capacity of membrane to concentrate florescent dyes (carbocyanines) in respons e to a membrane potential variation following the addition of a K+ ion ophore, 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 mu M and maximal at 1 mu M. These results seem to indicate that the chemical s eries of the GMS-010F presents a potent growth inhibitory activity of a highly tumorigenic gastric cancer cell line. The presence of a quate rnary ammonium group, responsible for some alkylating effect, could ex plain such a result.