FAMESYLAMINE - AN INHIBITOR OF FAMESYLATION 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 mediu m, 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 c ell extracts and also inhibited the prenylation of proteins, particula rly ras p21, in PAP2 cells. Inhibition of prenylation was associated w ith increased biosynthesis of other products of the mevalonate biosynt hetic pathway. These observations suggest that inhibition of the growt h of PAP2 cells by farnesylamine may be due to blocking of ras-mediate d signal transduction. This offers a means of investigating mechanisms involved in ras action and raises the possibility of developing novel strategies for anticancer therapy.