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 essential fatty acid (EFA) metabolites occurs in malignant cells and that gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) exert antimutagenic effects, the effects of GLA and EPA on UK activity have been investigated in this study. Both GLA (n-6) and EPA (n-3) acted as competitive inhibitors of UK with Ki values of 120 and 96 microM 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 decreased EFA concentrations show increased UK activity. The addition of EFAs to available therapeutic regimens may be worth considering in the treatment of cancer.