INHIBITION OF CARCINOMA AND MELANOMA CELL-GROWTH BY TYPE-1 TRANSFORMING GROWTH-FACTOR-BETA IS DEPENDENT ON THE PRESENCE OF POLYUNSATURATED FATTY-ACIDS

Improved serum-free media were developed for the anchorage-dependent growth of A549 human lung carcinoma and B16 mouse melanoma cell lines in vitro. Type 1 transforming growth factor β (TGF-β1) inhibited the growth of A549 or B16 cells under serum-free conditions or in the presence of 10% serum by 15-33%. In contrast, in the presence of μg/ml concentrations of polyunsaturated fatty acids (PUFAs), picomolar concentrations of TGF-β1 irreversibly inhibited the serum-free growth of A549 or B16 cells by 90-100%. The PUFAs alone had little effect on cell growth. Cell growth inhibition by TGF-β1 was not potentiated by saturated fatty acids, monounsaturated fatty acids, or prostaglandins. Inhibition of A549 or B16 cell growth by TGF-β1 in the presence of PUFAs was almost completely reversed by the antioxidant vitamin E, suggesting a role for lipid peroxidation in this process. Inhibition of A549 or B16 cell growth by TGF-β1 in the presence of 5% fetal calf serum was also potentiated by PUFAs and partially reversed by antioxidants. The presence of retinoic acid was required for maximal PUFA-dependent growth inhibition of A549 or B16 cells by TGF-β1 under some, but not all, conditions. These results suggest that inhibition of carcinoma and melanoma cell growth by TGF-β1 is mediated, in large part, by PUFAs.