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Title: Cancer chemopreventive properties of anthocyanins in patients with colorectal cancer and colorectal liver metastases
Author: Thomasset, Sarah Carol
ISNI:       0000 0004 2683 2382
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2009
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Anthocyanins, polyphenolic phytochemicals which render fruit and vegetables bright red or blue, possess anticarcinogenic properties in preclinical models of carcinogenesis. The aim of this study was to elucidate whether consumption of mirtocyan, a standardised anthocyanin extract, would cause pharmacodynamic changes consistent with chemoprevention and generate measurable levels of anthocyanins in blood, urine and target tissue. Twenty-five patients with either primary colorectal cancer or colorectal liver metastases received 1.4, 2.8 or 5.6 g of mirtocyan (containing 0.5-2.0 g anthocyanins) daily for 7 days prior to colon/liver resection. Anthocyanin levels were measured by high performance liquid chromatography. Proliferation (Ki-67), apoptosis (caspase-3) and inflammation (COX-2) were measured in colorectal tumour tissue. Effects on the insulin-like growth factor (IGF) axis were evaluated in plasma and markers of oxidative DNA damage were assessed in blood and urine. Consumption of up to 5.6 g of mirtocyan daily was well tolerated. Analysis of colorectal tumour tissue revealed that consumption of mirtocyan was associated with a 7% decrease in proliferation (p=0.003) and a 1.7% increase in apoptosis (0.044). A trend towards a reduction in circulating IGF-1 levels was observed (p=0.168). Mirtocyan anthocyanins and methyl and glucuronide metabolites were identified in plasma, urine and colorectal tissue, but not in liver. Anthocyanin concentrations in biomatrices were approximately dose-dependent. Following consumption of 5.6 g of mirtocyan daily anthocyanin levels in plasma, urine and colorectal tumour tissue were 117 ng/ml, 3 μg/ml and 179 ng/g, respectively. Mirtocyan did not affect levels of COX-2 or markers of oxidative DNA damage. Administration of mirtocyan furnished levels of anthocyanins in colorectal tumour tissue comparable to those capable of mediating chemopreventive effects in vivo. Consumption of only 1.4 g of mirtocyan daily may exert pharmacodynamic effects commensurate with colorectal cancer chemoprevention. These data support further clinical development of anthocyanins as potential colorectal cancer chemopreventive agents.
Supervisor: Gescher, A. ; Steward, W. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available