d-limonene chemoprevention of hepatocarcinogenesis in AKR mice: inhibition of c-jun and c-myc.

We have studied the chemopreventive effect of d-limonene, a monoterpene monocyclic compound, against N-nitrosodiethylamine (NDEA) alone and along with phenobarbital (PB) induced hepatocarcinogenesis in AKR mice. Histopathological analysis clearly indicates the maintenance of normal features when the mice were given limonene 15 days prior to carcinogen treatment. The immunohistochemical analysis of c-jun and c-myc oncoprotein shows an increased protein expression (2-3 fold) in NDEA and NDEA-PB mediated hepatocarcinogenesis after 60 days of NDEA treatment. Our earlier work by northern blot analysis has already indicated an increased transcription of c-jun and c-myc in NDEA mediated hepatocarcinogenesis. However, such overexpression of c-myc and c-jun both at mRNA and oncoprotein levels has been completely inhibited when d-limonene was used along with NDEA or NDEA-PB. Thus, the present investigation explains the anti-tumour effect of d-limonene for the first time on the level of oncogene expression in NDEA and NDEA-PB mediated hepatocarcinogenesis.