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Title: The biological activity of sulforaphane and iberin
Author: Chambers, Karen F.
ISNI:       0000 0004 2672 4699
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2008
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Diets rich in cruciferous vegetables· are associated with a reduced risk of cancer. This reduction in risk may be attributed to isothiocyantes (lTCs), which are the degradation products of glucosinolates. Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SF) is the predominant ITC formed from heading broccoli ('calabrese') and iberin (3-methylsulphinyl propyl isothiocyanate) is the predominant ITC formed from purple sprouting broccoli. While, there are many studies regarding the biological activity of SF, there are few studies associated with iberin. Moreover, the majority of studies have been undertaken with transformed cells, usually epithelial in origin, that have cancerous phenotypes. In this study, primary epithelial and fibroblast cells derived from benign prostatic hyperplasia tissue (BPH) were used as a more appropriate model of normal prostate tissue. There are thought to be. complex interactions between epithelial and fibroblast .cells during the initiation and progression of prostate cancer. Affymetrix array was used to report global gene expression changes in both primary fibroblast and epithelial cells on exposure to physiologically appropriate concentrations ofSF and iberin. The majority of genes altered between iberin and SF treated cells were different; however, according to GenMAPP analysis, these genes were involved in some ofthe same pathways. Genes altered by both iberin and SF fitted into four main gene ontology categories: xenobiotic metabolism, cell cycle arrest, apoptosis and oxidative stress. A number ofgenes from these categories were selected for real time RT-PCR analysis, which showed a novel increase in gene expression on iberin and SF exposure. These genes were eyelin-dependent kinase inhibitor lA (p21wafllCipl), kruppel-like factor 4 (KLF4), pleiomorphic adenoma gene-like 1 (PLAGLl), tumour necrosis factor receptor super family, member lOb (TNFRSFlOb) and thioredoxin reductase 1 (TrxRl). This study is also the first evidence that iberin and SF reduce the mRNA expression of interferon induced transmembrane protein (lFITMl), chondroitin sulfate proteoglycan 2 (CSPG2) and vimentin (VIM) in prostate epithelial cells. Histone acetylation was investigated as a mechanism of global gene control by SF and iberin, however there was inconsistent evidence that either isothiocyante controls gene expression through histone deacetylase inhibition.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available