MONOTERPENES IN BREAST-CANCER CHEMOPREVENTION

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 mamma ry cancer during the initiation phase as well as the promotion/progres sion phase. Similarly, the monoterpenoids carveol, uroterpenol, and so brerol have chemopreventive activity against mammary cancer when fed d uring the initiation phase. d-limonene and perillyl alcohol, a more po tent analog of Limonene, also have chemotherapeutic activity against r odent mammary and pancreatic tumors. As a result, their cancer chemoth erapeutic 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 carcinogenes is are due to the induction of Phase II carcinogen-metabolizing enzyme s, resulting in carcinogen detoxification. The post-initiation phase c hemopreventive 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 gr owth-regulating proteins. Thus, monoterpenes act through multiple mech anisms in the chemoprevention of mammary and other cancers.