Influence of the flavonoid (+)-catechin on the permeability of Ehrlich mouse ascites tumour cell membranes.
The effect of the flavonoid (+)-catechin and its hydrophilic derivative epicatechinsulphonate on the permeability of Ehrlich mouse ascites tumour cells (EMAT) was investigated. As a sensitive assay, the transmembrane fluxes of two different solutes were measured, the inwardly directed free diffusion of 14C-thiourea, and the carrier-mediated efflux of intracellularly accumulated 12C-1-aminocyclopentane-1-carboxylic acid. (+)-Catechn was found to reduce the permeability of EMAT membranes for both solutes. The primary target of the drug appears to be the membrane itself. The effectiveness of the drug was dependent on its concentration. Inhibition of fluxes was observed at 0.86 mM; the inhibition gradually increased as the concentration was increased. In contrast to (+)-catechin, epicatechinsulphonate was rather ineffective, even at a concentration as large as 10 mM. The effect of (+)-catechin was seen within a few minutes after its addition. However, it was considerably intensified as the incubation was prolonged. The effectivity of (+)-catechin decreased with increasing cell density. Thus, the drug appears to be absorbed by the cells. From the various data and the observation that incorporation of a strong lipophobic sulphonate residue into the moderately lipophilic catechin molecule markedly lowers the effectivity of the flavonoid, it is concluded that (+)-catechin, as a membrane stabilizing drug, interacts directly with certain constituents of the cell envelope, presumably membrane lipids.
D000327:Adsorption; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003515:Cycloleucine / Q000378:metabolism; D004058:Diffusion; D005260:Female; D051379:Mice; D013890:Thiourea / Q000378:metabolism
D001578:Benzopyrans; D003515:Cycloleucine; D002392:Catechin; D013890:Thiourea