Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 60, Issue 9, Pages 1924-1932Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201500989
Keywords
Apoptosis; Cell cycle arrest; Colon cancer; Metabolite; Pinostilbene; Pterostilbene
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Funding
- USDA
- China Scholarship Council
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Scope: Pterostilbene (PTE) is a resveratrol derivative mainly found in blueberries, and it has been shown to inhibit colon carcinogenesis in multiple animal models. To shed light on the mechanism of PTE in inhibiting colon carcinogenesis, we investigated the PTE metabolites in the mouse colon and in the human colon cancer cells. Methods and results: CD-1 mice were fed PTE-containing diet for 3 weeks, and colonic content and colonic mucosa were collected and subjected to LC-MS analysis. Pinostilbene (PIN) was identified as a major metabolite of PTE in the mouse colon. Importantly, the level of PIN was found to be approximately equivalent to that of PTE in the colonic mucosa. PIN significantly inhibited the growth of human colon cancer cells, i.e., HCT116 and HT29. These inhibitory effects were similar to those produced by PTE. Moreover, under physiologically relevant conditions, 20 and 40 mu M of PIN caused cell cycle arrest at S phase and induced apoptosis in colon cancer cells. These effects were associated with profound modulation of signaling proteins related with cell proliferation and programmed cell death. Conclusion: Our results demonstrated that PIN is a major metabolite of PTE in the colon of mice fed with PTE, and PIN may play important roles in the anti-colon cancer effects elicited by orally administered PTE.
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