Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice

Yi Siou Chiou, Mei Ling Tsai, Ying-Jan Wang, An Chin Cheng, Wei Ming Lai, Vladimir Badmaev, Chi Tang Ho, Min Hsiung Pan

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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 GSK3β phosphorylation and Wnt/β-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.

Original languageEnglish
Pages (from-to)8833-8841
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume58
Issue number15
DOIs
Publication statusPublished - 2010 Aug 11

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Fingerprint

Dive into the research topics of 'Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice'. Together they form a unique fingerprint.

Cite this