EXPLORING THE ROLE OF SULFORAPHANE IN PROSTATE METABOLISM

Al Kadhi, Omar (2017) EXPLORING THE ROLE OF SULFORAPHANE IN PROSTATE METABOLISM. Doctoral thesis, University of East Anglia.

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Abstract

Prostate cancer is a worldwide health problem with a higher incidence in older men. Prostate cancer risk is lower in Asian countries compared to the west, this has largely been attributed to difference in diets between the two populations. To date evidence from casecontrol studies has indicated that cruciferous vegetables and regular exercise reduce the risk of prostate cancer progression; however, other similar studies have shown no association. These contrasting results may be due to study heterogeneity and the long latent period of prostate cancer.

The aim of the work presented in this thesis is to further understand the role of sulforaphane, an isothiocyanate derived from broccoli plants in preventing prostate cancer by exploring its effect on the metabolic microenvironment of the prostate. One of the key metabolic pathways that is altered in prostate cancer is the Krebs� cycle. Citrate, a product of the Krebs� cycle accumulates in healthy prostate tissue and is reduced in prostate cancer. It was demonstrated by using a novel liquid chromatography and tandem mass spectrometry method that the levels of citrate within in vitro models of prostate cancer are markedly different to those of human tissue. Furthermore, citrate levels altered when prostate cells were exposed to reactive oxygen species. The addition of physiological quantities of sulforaphane to prostate cells in culture inhibited the reactive oxygen speciesmediated changes on the Krebs� cycle.

A randomised, double-blinded human intervention study was undertaken to further understand the role of sulforaphane in prostate cancer by recruiting men with early prostate cancer into three different study arms delivering sulforaphane in increasing concentrations through naturally bred broccoli varieties. A subgroup analysis demonstrated significant metabolite changes in prostate tissue that were driven by the study diet with accumulation of sulfate common to all three arms. This was positively correlated with lower rates of cancer at 12 months.
The work presented here strengthens the argument that sulforaphane in physiologically achievable concentrations can alter the metabolic environment of the prostate and that this may contribute to the cancer preventing properties of cruciferous vegetables.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Bruce Beckett
Date Deposited:	26 Jul 2018 10:54
Last Modified:	07 Sep 2018 10:18
URI:	https://ueaeprints.uea.ac.uk/id/eprint/67871
DOI:

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