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 beta (TGF-beta 1) 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 micrograms/ml concentrations of polyunsaturated fatty acids (PUFAs), picomolar concentrations of TGF-beta 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-beta 1 was not potentiated by saturated fatty acids, monounsaturated fatty acids, or prostaglandins. Inhibition of A549 or B16 cell growth by TGF-beta 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-beta 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-beta 1 under some, but not all, conditions. These results suggest that inhibition of carcinoma and melanoma cell growth by TGF-beta 1 is mediated, in large part, by PUFAs.
Newman
M J
MJ
Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110.
D000818:Animals; D002277:Carcinoma; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008175:Lung Neoplasms; D008546:Melanoma, Experimental; D051379:Mice; D010169:Palmitic Acids / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects; D014815:Vitamins / Q000494:pharmacology
D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D010169:Palmitic Acids; D013229:Stearic Acids; D014815:Vitamins; C008757:palmitoleic acid; C031183:stearic acid; D015291:Transforming Growth Factors; D019787:Linoleic Acid