The naturally occurring monoterpene d-limonene has chemopreventive and
chemotherapeutic activity against many rodent solid tumor types. The
chemopreventive activity of limonene during initiation can be attribut
ed to the induction of phase I and phase II enzymes, with resulting ca
rcinogen detoxification. The chemopreventive activity of limonene duri
ng promotion/progression may be due in part to inhibition of the postt
ranslational isoprenylation of growth-controlling small G proteins, su
ch as p21ras. The complete regression of mammary carcinomas by limonen
e appears to involve tissue redifferentiation. The multiple antitumori
genic effects of limonene are attainable at a high therapeutic ratio,
suggesting that limonene and related monoterpenes may be efficacious i
n the chemoprevention and chemotherapy of human malignancies.