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Pilot Study of Oral Anthocyanins for Colorectal Cancer Chemoprevention

By Sarah Thomasset, David P. Berry, Hong Cai, Kevin West, Tim H. Marczylo, Debbie Marsden, Karen Brown, Ashley Dennison, Giuseppe Garcea, Andrew Miller, David Hemingway, William P. Steward and Andreas J. Gescher

Abstract

This paper was published as Cancer Prevention Research, 2009, 2 (7), pp. 625-633. It is available from http://cancerpreventionresearch.aacrjournals.org/content/2/7/625. DOI: 10.1158/1940-6207.CAPR-08-0201Metadata only entryNaturally occurring anthocyanins possess colorectal cancer chemopreventive properties in rodent models. We investigated whether mirtocyan, an anthocyanin-rich standardized bilberry extract, causes pharmacodynamic changes consistent with chemopreventive efficacy and generates measurable levels of anthocyanins in blood, urine, and target tissue. Twenty-five colorectal cancer patients scheduled to undergo resection of primary tumor or liver metastases received mirtocyan 1.4, 2.8, or 5.6 grams (containing 0.5-2.0 grams anthocyanins) daily for 7 days before surgery. Bilberry anthocyanins were analyzed by high performance liquid chromatography (HPLC) with visible or mass spectrometric detection. Proliferation was determined by immunohistochemistry of Ki-67 in colorectal tumor. Concentrations of insulin-like growth factor (IGF)-I were measured in plasma. Mirtocyan anthocyanins and methyl and glucuronide metabolites were identified in plasma, colorectal tissue, and urine, but not in liver. Anthocyanin concentrations in plasma and urine were roughly dose-dependent, reaching ∼179 ng/gram in tumor tissue at the highest dose. In tumor tissue from all patients on mirtocyan, proliferation was decreased by 7% compared with preintervention values. The low dose caused a small but nonsignificant reduction in circulating IGF-I concentrations. In conclusion, repeated administration of bilberry anthocyanins exerts pharmacodynamic effects and generates concentrations of anthocyanins in humans resembling those seen in ApcMin mice, a model of FAP adenomas sensitive to the chemopreventive properties of anthocyanins. Studies of doses containing <0.5 gram bilberry anthocyanins are necessary to adjudge whether they may be appropriate for development as colorectal cancer chemopreventive agents

Topics: anthocyanins, bilberry, chemoprevention, dose response, drug development
Publisher: American Association for Cancer Research
Year: 2009
DOI identifier: 10.1158/1940-6207.CAPR-08-0201
OAI identifier: oai:lra.le.ac.uk:2381/9487
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