A number of dietary monoterpenes have chemopreventive activity against rat mammary cancer. For example, d-limonene, which comprises over 90% of orange peel oil, has chemopreventive activity against rodent mammary cancer during the initiation phase as well as the promotion/progression phase. Similarly, the monoterpenoids carveol, uroterpenol, and sobrerol have chemopreventive activity against mammary cancer when fed during the initiation phase. d-limonene and perillyl alcohol, a more potent analog of Limonene, also have chemotherapeutic activity against rodent mammary and pancreatic tumors. As a result, their cancer chemotherapeutic activities are under evaluation in Phase I clinical trials. Several mechanisms of action may account for the antitumor activities of monoterpenes. The blocking chemopreventive effects of limonene and other monoterpenes during the initiation phase of mammary carcinogenesis are due to the induction of Phase II carcinogen-metabolizing enzymes, resulting in carcinogen detoxification. The post-initiation phase chemopreventive and chemotherapeutic activities of monoterpenes may be due to the induction of tumor cell apoptosis, tumor redifferentiation, and/or inhibition of the post-translational isoprenylation of cell growth-regulating proteins. Thus, monoterpenes act through multiple mechanisms in the chemoprevention of mammary and other cancers.
