The monoterpene d limonene inhibit the plasma membrane associated P21 ras expression and the posttranslational isoprenylation of P21 ras

a mechanism that may contribute to its efficacy in the chemoprevention and therapy of chemically induced rodent cancers and some human solid tumor cells. In the present study

the relative abilities of d limonene to inhibit membrane associated P21 ras expression in pancreas tumor cell（PaCa） was carried out with Western blotting

and the inhibition of farnesyl protein transferase （FTPase） activity during the Ras protein isoprenylation and cell proliferation were determined.Concomitantly

the effects of d limonene on P21 ras localization by immunohistochemistry and H ras oncogene expression in PaCa tumor cell line by Northern blotting were observed. The results showed that d limonene inhibited FPTase activity

thus to reduce P21H ras isoprenylation. d limonene could decrease P21 ras membrane association and increase cytosolic accumulation of P21 ras . This phenomenon was also noted when d limonene treated PaCa cells were stained immunohistochemically with anti P21 ras antibody. It is suggested that the inhibition of FPTase activity was closely related with the inhibiton of P21 ras membrane association and the alteration of P21 ras localization. Inhibition of farnesylation of P21 ras altered their intracellular localization and

hence

disrupted their biological activity

but no relationship with H ras oncogene expression was found.