Cytotoxicity studies of quercetin, shikimate, cyclohexanecarboxylate and ptaquiloside

A study was carried out to determine the cytotoxic effects of quercetin, shikimate, cyclohexane-carboxylate and ptaquiloside on Chinese hamster ovary (CHO), mouse fibroblast (3T3) and normal rat kidney (NRK) cells by cell growth inhibition assay of monolayers grown in 96-well plates. Molar concentrations inhibiting cell growth by 50% (IC50) after 48 h of incubation for quercetin, shikimate, cyclohexanecarboxylate and ptaquiloside were 0.8 x 10(-4)M, 0.8 x 10(-3)M, 0.4 x 10(-2) M and 0.6 x 10(-1)M respectively for CHO cells; 1.2 x 10(-4)M, 0.7 x 10(-3)M, 0.2 x 10(-7)M and 0.6 x 10(-1)M respectively for 3T3 cells; and 0.7 x 10(-4)M, 1.0 x 10(-3)M, 0.2 x 10(-2)M and 0.6 x 10(-1)M respectively for NRK cells. These inhibiting concentrations were extremely high when compared with mitomycin C whose cytotoxic effect occurred at 1 x 10(-6)M. Cyclohexanecarboxylate is a metabolite of shikimate; any possible cytotoxic effect of shikimate in vivo may be mediated by the major metabolite cyclohexanecarboxylate per se or after futher metabolism of this metabolite following absorption in animals. Quercetin, ptaquiloside and shikimate are constituents of bracken fern. The low order of cytotoxic activity of these constituents suggest that they are probably not directly the etiological agents of acute cattle bracken fern poisoning.