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.