Title: Effects of Broccoli-Derived Sulphur Compounds on the Prostate Microenvironment

Coode-Bate, Jack (2017) Title: Effects of Broccoli-Derived Sulphur Compounds on the Prostate Microenvironment. Doctoral thesis, University of East Anglia.

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Epidemiological studies suggest a negative association between prostate cancer risk and dietary intake of cruciferous vegetables. These vegetables have a characteristic sulphur metabolism, delivering specialised compounds including glucosinolates, such as glucoraphanin, and S-methyl cysteine sulfoxide (SMCSO). An interim analysis of ongoing clinical trials at Quadram Institute Bioscience suggested an increase in inorganic sulphate, adenosine 5’-diphosphate (ADP) and potential antioxidant capacity of prostate tissue following broccoli consumption.

Sulforaphane, a hydrolytic product of glucoraphanin, influences multiple pathways relevant to prostate cancer prevention. Furthermore, degradation of SMCSO produces reactive intermediates, which induce apoptosis in prostate cancer cells, and ultimately yields high proportions of inorganic sulphate in human metabolism. Sulphate is likely to drive synthesis of phosphoadenosine 5’-phosphosulphate. Adenosine 5’-triphosphate (ATP) fuels this process, producing ADP and phosphate. As cancerous cells are unable to adjust their metabolism, depleting ATP by diet could prove an effective strategy for cancer prevention.

A high-dose, randomised, parallel-unblinded broccoli-intervention study was carried out in men awaiting trans-perineal prostate biopsies. Global metabolomic and targeted metabolite analyses were undertaken on prostate, adipose and urine samples to test the biological availability and activity of sulphur-containing metabolites from the study diet. In vitro experiments were undertaken to investigate the effects of sulforaphane and SMCSO on real-time prostate bioenergetics and redox status of proteins relevant to prostate cancer. S

MCSO was present at significantly higher levels (p<0.01) in both the urine and prostates of men receiving a broccoli-enriched diet. Whereas sulforaphane and its conjugates were undetectable in tissue. Levels of ATP and sulphate were not different between study groups. At physiological concentrations neither sulforaphane nor SMCSO affected mitochondrial function or redox status in vitro.

SMCSO accumulation in tissue after broccoli consumption may mediate the putative effects of cruciferous vegetables towards prostate cancer prevention through its degradation to highly-reactive intermediate products.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Bruce Beckett
Date Deposited: 23 Jul 2018 11:08
Last Modified: 23 Jul 2018 11:08
URI: https://ueaeprints.uea.ac.uk/id/eprint/67789


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