Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cells

The effect of the tritepene, ursolic acid, on the proliferation of A431 hum an epidermoid carcinoma cells was studied. According to our investigations, ursolic acid is a potent inhibitor of A431 cell growth. Ursolic acid marke dly reduced A431 cell growth in a time- and dose- dependent manner. We foun d a good correlation between the results of direct cell counting and the MT T test. During long periods of drug exposure, ursolic acid exhibited both c ytotoxic and cytostatic activity. The effect was partially reversible on dr ug I removal. The greatest cytotoxicity was observed both in the trypan blu e test and in the MTT test at 50 mM. investigations on tyrosine kinase inhi bition were performed by biochemical and cellular assays on A431 cells. Urs olic acid inhibited tyrosine kinase activity of A431 cells in biochemical a ssay in a dose- dependent manner with an IC50 of 24 mM. In cellular assay, when A431 cells were pretreated with ulsolic acid for 24, 48 and 168 hours at various concentrations (5, 10 24 30 and 50 mM), lower values of IC50 wer e measured: 6.8 muM for 24 hours, 5.2 mM for 48 hours and 1.4 mM for 168 ho urs. The results suggest that ursolic acid exerts an antiproliferative effe ct through the inhibition of tyrosine kinase enzymes.