Effects of long-chain fatty amines on the growth of ras-transformed NIH 3T3 cells

• Published in: Biochemical pharmacology Vol. 47; no. 10; p. 1909
• Main Authors: Kothapalli, R, Lui, E M, Guthrie, N, Chambers, A F, Carroll, K K
• Format: Journal Article
• Language: English
• Published: England 18-05-1994
• Subjects: 3T3 Cells - drug effects; Amines - pharmacology; Animals; Calcium - metabolism; Cell Division - drug effects; Cell Line, Transformed - drug effects; Farnesol - analogs & derivatives; Farnesol - pharmacology; Fatty Acids - pharmacology; Genes, ras; Mice; Protein Kinase C - antagonists & inhibitors
• ISSN: 0006-2952
• DOI: 10.1016/0006-2952(94)90322-0

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 (C12 to C18) were growth inhibitory, whereas short-chain amines (C6, C8) were not. Farnesylamine, a branched-chain, unsaturated amine (C15), had an IC50 of 6.9 microM compared to IC50 values of 13.1 to 45.8 microM for straight-chain, saturated amines. Oleylamine, with an IC50 of 0.1 microM, 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.