Epidemiological studies suggest that consumption of diets containing fruits and vegetables, major sources of
phytochemicals and
micronutrients, may reduce the risk of developing
cancer of the colon. Several
phytochemicals and
micronutrients present in fruits and vegetables are known to exert
cancer-chemopreventive effects in several organs, including the colon.
Monoterpenes such as
d-limonene and
perillyl alcohol derived from orange peels and lavender, respectively, have been shown to possess chemopreventive properties against mammary, liver, and/or lung
carcinogenesis. The present study was designed to investigate the efficacy of dietary 40 and 80% maximum tolerated dose (MTD) levels of
perillyl alcohol on
azoxymethane (AOM)-induced colon
carcinogenesis. The effect of this agent on the process of apoptosis in colon
tumors was also investigated. Prior to the efficacy study, the MTD of
perillyl alcohol was determined in male F344 rats in a 6-week subchronic toxicity study and found to be a 2.5-g/kg diet when added to the AIN-76A diet. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or diets containing 1 and 2 g
perillyl alcohol/kg diet, representing 40 and 80% MTD levels, respectively. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c.
injections of AOM (15 mg/kg
body weight/week). All animals were continued on their respective dietary regimen for 52 weeks after AOM treatment and then sacrificed. Colon
tumors were evaluated histopathologically using routine procedures.
Perillyl alcohol at the 1-g/kg level significantly inhibited the incidence (percentage of animals with
tumors) and multiplicity (
tumors/ animals) of invasive
adenocarcinomas of the colon, whereas
perillyl alcohol at 2 g/kg diet inhibited the incidence of total
adenocarcinomas of the colon and small intestine as compared to the control diet. Our studies also indicate that the colon
tumors of animals fed
perillyl alcohol exhibited increased apoptosis as compared to those fed the control diet. These results demonstrate the potential chemopreventive activity of
perillyl alcohol against colon
carcinogenesis. The chemopreventive activity of
perillyl alcohol is mediated through the
tumor cell loss by apoptosis.