EFFECTS OF URSOLIC ACID AND ITS ANALOGS ON SOYBEAN 15-LIPOXYGENASE ACTIVITY AND THE PROLIFERATION RATE OF A HUMAN GASTRIC TUMOR-CELL LINE

THE authors have previously isolated and purified ursolic acid from he ather flowers (Calluna vulgaris). This terpene was found to inhibit HL -60 leukaemic cell proliferation and arachidonic acid oxidative metabo lism in various cell species. The effects of ursolic acid and its anal ogues on soybean 15-lipoxygenase activity and on the proliferation of a human gastric tumour cell line (HGT), have been assessed. These trit erpenes inhibited soybean 15-lipoxygenase at its optimal activity (PH 9). The proliferation of HGT was decreased in a dose-dependent manner. At 20 muM the rank order is: ursolic acid > uvaol > oleanolic acid > methyl ursolate. The carboxylic group at the C28 position of ursolic a cid appears to be implicated in the inhibition of both lipoxygenase ac tivity and cell proliferation. Thus methylation of this group decrease s these two inhibitory properties. Oleanolic acid, which differs by th e position of one methyl group (C20 instead of C19) is less inhibitory than ursolic acid. The lipophilicity of the terpene is also implicate d since uvaol appears to be more inhibitory than methyl ursolate.