Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras P21proteins) in order to extend their biological activity. Previous studies indicated that an intermediate in mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group, that using inhibitors of the mevalonate pathway could block the transforming properties of ras oncogene. Unfortunately, mevalonate is the precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we partially purified farnesyl protein transferase (FPTase) capable of catalyzing the farnesylation of unprocessed Ras P21proteinsin vitrofrom porcine kidney epithelial-like LLC-PK1 cells, human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells. We observed the effects of the monoterpene compound, d-limonene (1); turmeric derivatives, TD-I (2) and TD-II (3); polyphenol compound, gallotannin; salviol derivative, SMD; and retinoid acid derivative, RAD on FPTase activity. We found that turmeric derivatives and gallotannin had a strong inhibition on FPTase besides d-limonene, while gallotannin was the strongest among synthetic and natural compounds tested. Saliviol and retinoid acid derivatives had no influence on FPTase activity. Our results suggest that compounds containing polyphenol hydroxyl may be a new source of FPTase inhibitors. The experiment also showed that availability of anin vitroFPTase assay could be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.