Chemoprevention and therapy of cancer by d-limonene.

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 attributed to the induction of phase I and phase II enzymes, with resulting carcinogen detoxification. The chemopreventive activity of limonene during promotion/progression may be due in part to inhibition of the posttranslational isoprenylation of growth-controlling small G proteins, such as p21ras. The complete regression of mammary carcinomas by limonene appears to involve tissue redifferentiation. The multiple antitumorigenic effects of limonene are attainable at a high therapeutic ratio, suggesting that limonene and related monoterpenes may be efficacious in the chemoprevention and chemotherapy of human malignancies.