Exploring the Role of Sulphur Compounds derived from Broccoli on Prostate Cancer Metabolism

Beasy, Gemma (2023) Exploring the Role of Sulphur Compounds derived from Broccoli on Prostate Cancer Metabolism. Doctoral thesis, University of East Anglia.

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Abstract

While diets rich in cruciferous vegetables such as broccoli have been shown to reduce prostate cancer risk and progression potentially due to the presence of sulfur-containing compounds, the role of the sulfur-containing compound S-methyl-L-cysteine sulfoxide (SMCSO) in cancer metabolism is relatively unexplored. A recent human study observed consumption of broccoli soups reduced fasting plasma glucose in men on active surveillance, however this was independent of the glucosinolate content. Since others have shown that SMCSO beneficially affects glucose metabolism in rodent models, it seems it is likely that SMCSO in the broccoli soups caused the observed reduction in fasting plasma glucose in the human study.

The overall aim of the research presented in this thesis was to investigate the effects of SMCSO and its metabolite S-methyl methanethiosulfonate (MMTSO) on prostate cancer energy metabolism, using cultured DU145 prostate cancer cells. This was explored through the use of the Seahorse Bioanalyser, RNA-sequencing and untargeted/targeted metabolomic analyses that observed changes in real-time mitochondrial energetics, gene expression, and global metabolomic profile respectively.

MMTSO and to a lesser extent SMCSO reduced mitochondrial metabolism, increased fatty acid dependency, upregulated gene expression of pathways associated with immune function and apoptosis including interleukin-2 signal transducer and activator of transcription-5 (IL2-STAT5), increased metabolite changes relating to the tricarboxylic acid (TCA) cycle, and decreased concentration of key non-essential amino acids. In addition, since there have been no randomised controlled trials that have investigated the potential effects of SMCSO on prostate cancer progression, products that could be suitable for future cancer human trials were assessed and characterised.

Overall, the evidence presented in this thesis demonstrated SMCSO and MMTSO are capable of modulating mitochondrial, transcriptomic and metabolomic profiles of DU145 prostate cancer cells, and may contribute to the reduction observed in prostate cancer progression following consumption of a broccoli-rich diet.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	12 Oct 2023 12:44
Last Modified:	12 Oct 2023 12:44
URI:	https://ueaeprints.uea.ac.uk/id/eprint/93276
DOI:

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