Farnesylamine: an inhibitor of farnesylation and growth of ras-transformed cells.
Farnesylamine, an analogue of farnesol, was shown to inhibit growth of PAP2 cells (ras-transformed NIH 3T3 cells) in a dose-dependent manner. This inhibition was overcome by adding farnesol to the culture medium, but not by adding geranylgeraniol, squalene, cholesterol, dolichol, myristic acid or palmitic acid. Farnesylamine inhibited both farnesyl/protein transferase and geranylgeranyl/protein transferase in whole cell extracts and also inhibited the prenylation of proteins, particularly ras p21, in PAP2 cells. Inhibition of prenylation was associated with increased biosynthesis of other products of the mevalonate biosynthetic pathway. These observations suggest that inhibition of the growth of PAP2 cells by farnesylamine may be due to blocking of ras-mediated signal transduction. This offers a means of investigating mechanisms involved in ras action and raises the possibility of developing novel strategies for anticancer therapy.
Kothapalli
R
R
Department of Biochemistry, University of Western Ontario, London, Canada.
Guthrie
N
N
Chambers
A F
AF
Carroll
K K
KK
D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002784:Cholesterol / Q000096:biosynthesis; D004286:Dolichols / Q000378:metabolism; D005204:Farnesol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D051379:Mice; D017368:Protein Prenylation / Q000187:drug effects*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D014166:Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis
D004286:Dolichols; D014451:Ubiquinone; D005204:Farnesol; C085171:farnesylamine; D002784:Cholesterol; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D016283:Proto-Oncogene Proteins p21(ras)