Analysis of grape anthocyanins and their biological properties in prostate cancer cells
Abstract
Anthocyanins are a group of flavonoid compounds that are believed to contribute to the prevention of certain chronic diseases when consumed as part of the daily diet. The overall aim of this thesis research was to identify and analyze the anthocyanins in red grapes and wines and determine the health promoting benefits provided by these molecules. The hypothesis for this research was that dietary flavonoids and n-3 polyunsaturated fatty acids (PUFA) have a potential synergism for modulating the activity of peroxisome proliferators activated receptors (PPARs) by acting as ligands and dependently reducing the transcription of cyclooxygenase-2 (COX-2). The candidate compounds may also work independently on transcription factors that may influence prostaglandin E2 (PGE2) production. Anthocyanins extracted from Indiana grown grapes and wines were found to be more abundant in the Norton variety than in Concord and Foch varieties. In addition, anthocyanin extracts from Norton grapes showed higher radical scavenging capacity than the other two grape varieties when measured by the DPPH test. Results revealed that Norton grapes may serve as a better source of potential antioxidants than Concord and Foch due to its higher content of total anthocyanins and greater radical scavenging capacity. The human prostate cancer cell line, LNCaP, was used as a model to determine the actions of the anthocyanin aglycon, cyanidin, and different PUFA in vitro. Results showed that COX-2 protein and mRNA levels were regulated by a negative feedback loop when arachidonic acid (AA) is present due to an increase in the PGE2, the AA metabolite. Moreover, AA promoted a higher number of viable cells than the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Cyanidin (0.1–1 μM) reduced the number of viable LNCaP cells. This concentration range would likely be achievable through diet. The reduction in cell growth may be due to a decrease in the production of PGE2, since cyanidin addition to the cell media presumably reduced PGE2 levels by reducing COX-2 activity. The results indicate that both PUFA and cyanidin influence COX-2 activity and the mediators of inflammation by serving as potential modulators of transcription factors of genes.
Degree
Ph.D.
Advisors
Watkins, Purdue University.
Subject Area
Food science
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