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 (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.
Kothapalli
R
R
Department of Biochemistry, University of Western Ontario, London, Canada.
Lui
E M
EM
Guthrie
N
N
Chambers
A F
AF
Carroll
K K
KK
D016475:3T3 Cells / Q000187:drug effects*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects; D005204:Farnesol / Q000031:analogs & derivatives / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D011905:Genes, ras; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors
D000588:Amines; D005227:Fatty Acids; D005204:Farnesol; C085171:farnesylamine; D011493:Protein Kinase C; D002118:Calcium; C008703:oleylamine