Yue Sun1,2, Xian Wu2, Xiaokun Cai2, Mingyue Song2, Jinkai Zheng2,3, Che Pan2, Peiju Qiu1,2, Lijuan Zhang1, Shuangde Zhou4, Zhonghai Tang4, Hang Xiao5,6. 1. School of Pharmacy, Ocean University of China, Qingdao, P. R. China. 2. Department of Food Science, University of Massachusetts, Amherst, MA, USA. 3. Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, P. R. China. 4. College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, P. R. China. 5. Department of Food Science, University of Massachusetts, Amherst, MA, USA. hangxiao@foodsci.umass.edu. 6. College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, P. R. China. hangxiao@foodsci.umass.edu.
Abstract
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 μM 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.
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 humancolon 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 humancolon 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 μM 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.
Authors: Ruth Hornedo-Ortega; Ana B Cerezo; Rocío M de Pablos; Stéphanie Krisa; Tristan Richard; M Carmen García-Parrilla; Ana M Troncoso Journal: Front Cell Neurosci Date: 2018-10-23 Impact factor: 5.505