Accumulation of Dietary S-Methyl Cysteine Sulfoxide in Human Prostate Tissue

Jack Coode-Bate, Tharsini Sivapalan, Antonietta Melchini, Shikha Saha, Paul W Needs, Jack R Dainty, Jean-Bapiste Maicha, Gemma Beasy, Maria H Traka, Robert D Mills, Richard Y Ball, Richard F Mithen, Jack Coode-Bate, Tharsini Sivapalan, Antonietta Melchini, Shikha Saha, Paul W Needs, Jack R Dainty, Jean-Bapiste Maicha, Gemma Beasy, Maria H Traka, Robert D Mills, Richard Y Ball, Richard F Mithen

Abstract

Scope: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates-thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli-derived metabolites in prostate tissue is tested.

Methods and results: Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4-week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup.

Conclusion: The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated.

Keywords: S-methyl cysteine sulfoxide; broccoli; cancer; glucosinolates; prostate.

Conflict of interest statement

The authors declare the following competing interests: R.F.M., M.H.T. and A.M. are co‐inventors in two patents (PCT/GB2017/050838, GB1605013.0) that cover combinations of a composition comprising glucoraphanin and SMCSO for the treatment or prevention of prostate cancer. The other authors declare no conflict of interest.

© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figures

Figure 1
Figure 1
a) 4‐Methylsulphinylbutyl glucosinolate (glucoraphanin) and its hydrolysis to the corresponding isothiocyanate, sulforaphane. b) S‐methylcysteine sulfoxide (SMCSO, methiin) and its degradation products. β‐eliminative enzymatic cleavage of SMCSO produces highly reactive methanesulfenic acid (equation (1)). Spontaneous nucleophilic attack of one molecule of methanesulfenic acid on another leads to the formation of S‐methyl methanethiosulfinate (IUPAC name methylsulfinylsulfanylmethane*, equation (2)). This can disproportionate (equation (3)) to form dimethyl disulfide and S‐methyl methanethiosulfonate (MMTS, IUPAC name methylsulfonylsulfanylmethane*). Nucleophilic attack of hydrogen sulfide (a known product of Brassica breakdown, though its genesis is unclear) on S‐methyl methanethiosulfinate gives disulfanylmethane, which can react in similar fashion with a second molecule of S‐methyl methanethiosulfinate to give dimethyl trisulfide (equation (4)). *Several, often inconsistent names and abbreviations have been used for these compounds.
Figure 2
Figure 2
Flow chart of pathways to recruitment.
Figure 3
Figure 3
The effect of heating soup to boiling on amount of a) glucoraphanin and b) SMCSO compared to unheated control by microwave or conduction heating. Columns are means of two independent samples.
Figure 4
Figure 4
a) SMCSO in prostate and b) SMCSO in peri‐prostatic tissue in control and supplement groups. p‐Values are from Student's t‐tests.
Figure 5
Figure 5
SMCSO is prostate and urine.
Figure 6
Figure 6
a) Sulfate in prostate tissue of control and supplement groups. b) Sulforaphane in urine of control and supplement groups. p‐Values are from Student's t‐tests.
Figure 7
Figure 7
SMCSO in two cores from four patients who had undergone radical prostatectomies.
Figure 8
Figure 8
a) SMCSO in plasma and b) in urine following consumption of single portion of broccoli soup at time 0. Points represent mean ± SD.
Figure 9
Figure 9
a) The concentration of SMCSO and glucosinolates in samples of cruciferous vegetables. Each bar represents level in pooled sample of vegetables purchased from retail outlet. The precise cultivars are unknown. b) Mean ± SD of three samples of leek, garlic, onion, and broccoli purchased from retail outlet. The cultivars are unknown.

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