A ferulic acid derivative, ethyl 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate, as a new candidate chemopreventive agent for colon carcinogenesis in the rat.
The inhibitory influence of ferulic acid (FA), a rice germ component, and its geranylated derivative 3-(4'-geranyloxy-3-methoxyphenyl)-2-propenoate (EGMP) on the post-initiation stage of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats given two s.c. injections of AOM (15 mg / kg body weight) during week 1. Diets containing EGMP or FA at doses of 0.1 or 0.2% were then fed for 3 weeks from week 2 to 5, when the animals were sacrificed. The numbers of aberrant crypt foci (ACF) and aberrant crypts (AC) per rat in the group given 0.2% FA were significantly decreased (P < 0.001) as compared to the AOM alone group. Furthermore, the numbers of ACF and AC per rat fed the 0.2% and 0.1% EGMP were significantly reduced (P < 0.001 and P < 0.01, respectively). Colonic epithelial cells in S-phase, as measured by bromodeoxyuridine (BrdU) labeling, in rats fed EGMP were significantly decreased in the 0.2 and 0.1% EGMP groups as compared to the AOM alone group (P < 0.05). BrdU labeling indices in rats fed FA and EGMP assessed by a test using a coefficient for linear contrast were also significantly decreased as compared to the AOM alone value (P < 0.05, P < 0.01, respectively). The results indicate that FA and EGMP have inhibitory effects on ACF and AC development, EGMP being more potent, possibly due to stronger suppressive effects on cell proliferation. No toxic effects were observed in rats given either compound in terms of body and organ weights, and liver or kidney histology. The findings thus suggest that EGMP and FA, especially the former, might have potential as chemopreventive agents against colon tumor development.
Han
B S
BS
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Park
C B
CB
Takasuka
N
N
Naito
A
A
Sekine
K
K
Nomura
E
E
Taniguchi
H
H
Tsuno
T
T
Tsuda
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D003373:Coumaric Acids / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D003373:Coumaric Acids; D013729:Terpenes; C403134:ethyl-3-(4'-geranyloxy-3'-methoxyphenyl)-2-propenoate; C004999:ferulic acid; D001973:Bromodeoxyuridine