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.