Pterostilbene, an Active Constituent of Blueberries, Suppresses Aberrant Crypt Foci Formation in the Azoxymethane-Induced Colon Carcinogenesis Model in Rats

Abstract

Purpose: 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. Experimental Design: 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 azoxymethaneinduced formation of ACF (57% inhibition, P < 0.001) and multiple clusters of aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene also suppressed azoxymethaneinduced 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.Stilbenes, such as resveratrol and pterostilbene, are a subset of naturally occurring phenolic compounds known to have diverse pharmacologic activities including cancer chemopreventive activity (1 -4). Stilbenes have been found in some berries (e.g., blueberries, cranberries, sparkleberries, lingonberries, and grapes; ref. 5), thus, consumption of these small fruits may help improve health. It is interesting that dietary black raspberries significantly suppressed N-nitrosomethylbenzylamine -induced rat esophageal carcinogenesis (6). The discovery of resveratrol as a cancer-preventive agent has fostered interest in testing the cancer-preventive activity of other naturally occurring stilbenes in many laboratories. Notably, pterostilbene, a dimethylether analogue of resveratrol, was found to be as effective as resveratrol in preventing carcinogeninduced preneoplastic lesions in a mouse mammary organ culture model (2). Additionally, i.v. administration of pterostilbene to mice inhibited metastatic growth of B16M-F10 melanoma cells in the liver, a common site for metastasis development (7).Pterostilbene and resveratrol have very similar pharmacologic properties (2,8). In addition to the aforementioned activity in the mouse mammary organ culture model, both compounds are strong antio...

Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials

“…2). Researchers have started to explore the anticancer effects of resveratrol derivatives in vivo (40,55,(73)(74)(75), and at least one study indicated that a tetramer of resveratrol (heyneanol) had comparable or better anticancer efficacy than did resveratrol in a mouse lung cancer model (55). However, more in vivo studies of head-to-head comparisons between resveratrol and its analogues are ongoing and no doubt will help elucidate the anticancer potential of specific compounds.…”

Combinatorial Biosynthesis of Non-bacterial and Unnatural Flavonoids, Stilbenoids and Curcuminoids by Microorganisms

“…For instance, 3,5-O-methylated stilbenes [pterostilbene (2l; Fig. 5) and 3-hydroxypetrostilbene] are better apoptosis-inducing agents towards several tumor cells [50,51] (Fig. 5).…”

A Stress-Inducible Resveratrol O-Methyltransferase Involved in the Biosynthesis of Pterostilbene in Grapevine

“…In addition, pterostilbene exhibits antioxidant and anticancer properties similar to those of resveratrol (Jang et al, 1997). Pterostilbene was found to be very effective in preventing carcinogeninduced preneoplastic lesions in a mouse mammary organ culture model (Rimando et al, 2002) and it showed preventive activity against colon carcinogenesis in rats (Suh et al, 2007).…”