Accumulation of sulphur-containing dietary bioactives and the impact on the transcriptional signature of the prostate

Livingstone, Tracey (2022) Accumulation of sulphur-containing dietary bioactives and the impact on the transcriptional signature of the prostate. Doctoral thesis, University of East Anglia.

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Abstract

Epidemiological evidence suggests that the consumption of sulphur-containing plant bioactives derived from cruciferous and alliaceous vegetables reduce the risk of prostate cancer incidence and progression.

The anti-cancer properties of cruciferous vegetables are largely attributed to the glucosinolate degradation product sulforaphane, which has a multi-modal effect on cancer pathways. Sulforaphane and its metabolites are documented to accumulate within the urine of patients consuming a high glucoraphanin diet but have not been shown to accumulate within the human prostate gland. Alliaceous vegetables also accumulate bioactive organosulphur compounds, namely the S-alk(en)yl-L-cysteine sulfoxides and γ-glutamyl S-allyl-L cysteines, which (along with their organosulphur metabolites) are attributed to a reduction in prostate cancer risk. Despite cell, animal and epidemiological evidence, there are currently no human intervention studies analysing the effect of alliaceous vegetables on prostate cancer.

39 men scheduled for transperineal prostate biopsies completed a randomised, 22 factorial design, double-blinded intervention study. Patients received high-dose dietary supplementation with myrosinase-activated glucoraphanin, alliin, and/or placebo, for at least 28 days prior to their procedure.

Free Sulforaphane was detected at significantly higher levels in the prostate of all patients consuming a glucoraphanin intervention (p<0.0001). The sulforaphane metabolite sulforaphane-N-acetylcysteine was detected at significantly higher concentrations in the peripheral zone of patients consuming glucoraphanin supplementation (p=0.0281) compared to a non-glucoraphanin intervention. S-allyl-L-cysteine was detected to significantly higher levels in the transition zone of patients consuming an Alliin intervention. Transcriptional analysis of the prostate demonstrated that the peripheral and transition zones possess unique transcriptional signatures, which may explain the differing propensity of the peripheral zone towards cancer. Both dietary compounds are capable of altering the transcriptional pathways associated with prostate cancer.

This is the first evidence for the accumulation of sulforaphane and alliin metabolites within the human prostate, whereby they subsequently influence a variety of oncogenic pathways to reduce prostate cancer risk.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	11 May 2022 13:23
Last Modified:	11 May 2022 13:23
URI:	https://ueaeprints.uea.ac.uk/id/eprint/84991
DOI:

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