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Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate

Traka M, Gasper AV, Melchini A, Bacon JR, Needs PW, Frost V, Chantry A, Jones AM, Ortori CA, Barrett DA, Ball RY, Mills RD, Mithen RF

PloS one · 103 citas

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Cómo se estudió

Diseño
Ensayo controlado aleatorizado (indexado por PubMed)
Estudiado en
Personas
Resultado principal
Solo mecanismos
Consumo medido con
No se indica

Quién lo pagó

Financiación
Financiación independiente
Universidad u hospital
University of Nottingham
Gobierno
Directorate for Biological Sciences
Gobierno
Biotechnology and Biological Sciences Research Council

Según 3 financiadores declarados y la declaración de financiación del texto completo.

Publicación

Publicado
2008-07-01 · PLoS One · vol. 3 · número 7 · pág. e2568
Editorial
Public Library of Science
Citado
154 citas · más que el 98% de estudios similares · 6.3× el promedio de su campo
Impacto
Entre el 10 % más citado de su campo
Referencias
51 trabajos
Acceso
Acceso abierto (revista) · CC-BY
Áreas de investigación
Genomics, phytochemicals, and oxidative stress · Glutathione Transferases and Polymorphisms · Nutrition, Genetics, and Disease
Palabras clave
broccoli, cruciferous vegetables, GSTM1 genotype, sulforaphane, isothiocyanates, prostate cancer, gene expression, EGF signaling, insulin signaling, androgen signaling, thiourea, dietary intervention, inflammation, carcinogenesis
MeSH
prostate, humans, brassica, prostatic neoplasms, glutathione transferase, diet, risk factors, signal transduction, models, biological, aged, middle aged, male

13 autores

  • Μαρία Τράκα🇬🇧Norwich Research Park; Quadram Institute
  • Amy V. Gasper🇬🇧Norwich Research Park; Quadram Institute
  • Antonietta Melchini🇮🇹🇬🇧University of Messina; Norwich Research Park; Quadram Institute
  • James Richard Bacon🇬🇧Norwich Research Park; Quadram Institute
  • Paul W. Needs🇬🇧Norwich Research Park; Quadram Institute
  • Victoria Jane Frost🇬🇧University of East Anglia
  • Andrew Chantry🇬🇧University of East Anglia
  • Alexandra M. E. Jones🇬🇧Norwich Research Park; Sainsbury Laboratory
  • Catharine A. Ortori🇬🇧University of Nottingham
  • David A. Barrett🇬🇧University of Nottingham
  • Richard Y. Ball🇬🇧Norfolk and Norwich University Hospital
  • Robert Mills🇬🇧Norfolk and Norwich University Hospital
  • Richard F. Mithen🇬🇧 · autor de correspondenciaNorwich Research Park; Quadram Institute

Resumen

El texto original del estudio, en el idioma en que se publicó.

Background

Epidemiological studies suggest that people who consume more than one portion of cruciferous vegetables per week are at lower risk of both the incidence of prostate cancer and of developing aggressive prostate cancer but there is little understanding of the underlying mechanisms. In this study, we quantify and interpret changes in global gene expression patterns in the human prostate gland before, during and after a 12 month broccoli-rich diet.

Methods and findings

Volunteers were randomly assigned to either a broccoli-rich or a pea-rich diet. After six months there were no differences in gene expression between glutathione S-transferase mu 1 (GSTM1) positive and null individuals on the pea-rich diet but significant differences between GSTM1 genotypes on the broccoli-rich diet, associated with transforming growth factor beta 1 (TGFbeta1) and epidermal growth factor (EGF) signalling pathways. Comparison of biopsies obtained pre and post intervention revealed more changes in gene expression occurred in individuals on a broccoli-rich diet than in those on a pea-rich diet. While there were changes in androgen signalling, regardless of diet, men on the broccoli diet had additional changes to mRNA processing, and TGFbeta1, EGF and insulin signalling. We also provide evidence that sulforaphane (the isothiocyanate derived from 4-methylsuphinylbutyl glucosinolate that accumulates in broccoli) chemically interacts with TGFbeta1, EGF and insulin peptides to form thioureas, and enhances TGFbeta1/Smad-mediated transcription.

Conclusions

These findings suggest that consuming broccoli interacts with GSTM1 genotype to result in complex changes to signalling pathways associated with inflammation and carcinogenesis in the prostate. We propose that these changes may be mediated through the chemical interaction of isothiocyanates with signalling peptides in the plasma. This study provides, for the first time, experimental evidence obtained in humans to support observational studies that diets rich in cruciferous vegetables may reduce the risk of prostate cancer and other chronic disease.

Trial registration

ClinicalTrials.gov NCT00535977.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

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