title: Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice.
abstract: Pterostilbene (PS), a natural dimethylated analogue of resveratrol, is known to have diverse pharmacologic activities including anticancer, anti-inflammation, antioxidant, apoptosis, antiproliferation, and analgesic potential. This paper reports the inhibitory effect of dietary administration of pterostilbene against the formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) preneoplastic lesions and adenomas in male ICR mice and delineates its possible molecular mechanisms. ICR mice were given two AOM injections intraperitoneal and continuously fed a 50 or 250 ppm pterostilbene diet for 6 or 23 weeks. It was found that the dietary administration of pterostilbene effectively reduced AOM-induced formation of ACF and adenomas and inhibited the transcriptional activation of iNOS and COX-2 mRNA and proteins in mouse colon stimulated by AOM. Treatment with pterostilbene resulted in the induction of apoptosis in mouse colon. Moreover, administration of pterostilbene for 23 weeks significantly suppressed AOM-induced GSK3beta phosphorylation and Wnt/beta-catenin signaling. It was also found that pterostilbene significantly inhibited AOM-induced expression of VEGF, cyclin D1, and MMPs in mouse colon. Furthermore, pterostilbene markedly inhibited AOM-induced activation of Ras, phosphatidylinositol 3 kinase/Akt, and EGFR signaling pathways. All of these results revealed that pterostilbene is an effective antitumor agent as well as its inhibitory effect through the down-regulation of inflammatory iNOS and COX-2 gene expression and up-regulation of apoptosis in mouse colon, suggesting that pterostilbene is a novel functional agent capable of preventing inflammation-associated colon tumorigenesis.
authors.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 811, Taiwan.
authors.forename: Yi-Siou
authors.initials: YS
authors.lastname: Chiou
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Tsai
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
authors.forename: An-Chin
authors.initials: AC
authors.lastname: Cheng
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Lai
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000009:adverse effects; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D013267:Stilbenes; C107773:pterostilbene; D001397:Azoxymethane