THE EFFECT OF GAMMA-LINOLENIC ACID AND EICOSAPENTAENOIC ACID ON UROKINASE ACTIVITY

Urokinase (UK) is an important protease enzyme in carcinogenesis, and is involved in the invasion and metastasis of cancer. Thus, regulation of UK activity is likely to be important in healthy cell metabolism. As it has been reported that a decrease in Delta 6-desaturated essenti al fatty acid (EFA) metabolites occurs in malignant cells and that gam ma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) exert antimuta genic effects, the effects of GLA and EPA on UK activity have been inv estigated in this study. Both GLA (n-6) and EPA (n-3) acted as competi tive inhibitors of UK with K-i values of 120 and 96 mu M respectively. No modification of plasmin activity occurred with either 1.4 x 10(4) M GLA or EPA. These results could explain why malignant cells with dec reased EFA concentrations show increased UK activity. The addition of EFAs to available therapeutic regimens may be worth considering in the treatment of cancer.