Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats.
OBJECTIVE
Epidemiologic studies have linked the consumption of fruits and vegetables to reduced risk of several types of cancer. Laboratory animal model studies have provided evidence that stilbenes, phenolic compounds present in grapes and blueberries, play a role in inhibiting the risk of certain cancers. Pterostilbene, a naturally occurring stilbene from blueberries, was tested for its preventive activity against colon carcinogenesis.


METHODS
Experiments were designed to study the inhibitory effect of pterostilbene against the formation of azoxymethane-induced colonic aberrant crypt foci (ACF) preneoplastic lesions in male F344 rats. Beginning at 7 weeks of age, rats were treated with azoxymethane (15 mg/kg body weight s.c., once weekly for 2 weeks). One day after the second azoxymethane treatment, rats were fed experimental diets containing 0 or 40 ppm of pterostilbene. At 8 weeks after the second azoxymethane treatment, all rats were sacrificed, and colons were evaluated for ACF formation and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen. Effects on mucin MUC2 were also determined.


RESULTS
Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane-induced formation of ACF (57% inhibition, P < 0.001) and multiple clusters of aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene also suppressed azoxymethane-induced colonic cell proliferation and iNOS expression. Inhibition of iNOS expression by pterostilbene was confirmed in cultured human colon cancer cells.


CONCLUSIONS
The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest for the prevention of colon cancer.
Suh
Nanjoo
N
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. nsuh@rci.rutgers.edu
Paul
Shiby
S
Hao
Xingpei
X
Simi
Barbara
B
Xiao
Hang
H
Rimando
Agnes M
AM
Reddy
Bandaru S
BS
D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology*; D029798:Blueberry Plants; D001835:Body Weight; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008956:Models, Chemical; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
C524625:MUC2 protein, human; C524628:Muc2 protein, rat; D055262:Mucin-2; D009077:Mucins; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D013267:Stilbenes; C107773:pterostilbene; D052247:Nitric Oxide Synthase Type II; D001397:Azoxymethane