EFFECTS OF LONG-CHAIN FATTY AMINES ON THE GROWTH OF RAS-TRANSFORMED NIH 3T3 CELLS

A number of aliphatic primary amines were tested for their effects on the growth of ras-transformed NIH 3T3 cells (PAP2 cells), as measured by incorporation of tritiated thymidine into DNA. Long-chain, saturated amines (C-12 to C-18) were growth inhibitory, whereas short-chain amines (C-6, C-8) were not. Farnesylamine, a branched-chain, unsaturated amine (C-15), had an IC50 of 6.9 mu M compared to IC50 values of 13.1 to 45.8 mu M for straight-chain, saturated amines. Oleylamine, with an IC50 of 0.1 mu M, was the most potent inhibitor. The long-chain amines, but not the short-chain amines, were also effective inhibitors of protein kinase C, assayed in vitro in a cell-free system. In addition, studies with indo-1-loaded PAP2 cells showed that long-chain amines induced a reversible rise in intracellular free Ca2+ concentration. Growth inhibition by the amines was positively correlated with this effect, suggesting that factors other than protein kinase C may be involved in the inhibition of growth of PAP2 cells by long-chain amines.