Proceedings of the National Academy of Sciences, Vol 87, 5543-5547, Copyright © 1990 by National Academy of Sciences

Inhibition of Carcinoma and Melanoma Cell Growth by Type 1 Transforming Growth Factor ß is Dependent on the Presence of Polyunsaturated Fatty Acids

MJ Newman
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 ß (TGF-ß1) 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 µ g/ml concentrations of polyunsaturated fatty acids (PUFAs), picomolar concentrations of TGF-ß 1 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-ß 1 was not potentiated by saturated fatty acids, monounsaturated fatty acids, or prostaglandins. Inhibition of A549 or B16 cell growth by TGF-ß 1 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-ß 1 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-ß 1 under some, but not all, conditions. These results suggest that inhibition of carcinoma and melanoma cell growth by TGF-ß 1 is mediated, in large part, by PUFAs.

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