PMID- 18596959
OWN - NLM
STAT- MEDLINE
DCOM- 20081022
LR  - 20240109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 7
DP  - 2008 Jul 2
TI  - Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling 
      pathways in the prostate.
PG  - e2568
LID - 10.1371/journal.pone.0002568 [doi]
LID - e2568
AB  - 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.
FAU - Traka, Maria
AU  - Traka M
AD  - Phytochemicals and Health Programme, Institute of Food Research, Norwich Research 
      Park, Norwich, United Kingdom.
FAU - Gasper, Amy V
AU  - Gasper AV
FAU - Melchini, Antonietta
AU  - Melchini A
FAU - Bacon, James R
AU  - Bacon JR
FAU - Needs, Paul W
AU  - Needs PW
FAU - Frost, Victoria
AU  - Frost V
FAU - Chantry, Andrew
AU  - Chantry A
FAU - Jones, Alexandra M E
AU  - Jones AM
FAU - Ortori, Catharine A
AU  - Ortori CA
FAU - Barrett, David A
AU  - Barrett DA
FAU - Ball, Richard Y
AU  - Ball RY
FAU - Mills, Robert D
AU  - Mills RD
FAU - Mithen, Richard F
AU  - Mithen RF
LA  - eng
SI  - ClinicalTrials.gov/NCT00535977
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080702
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.5.1.18 (glutathione S-transferase M1)
SB  - IM
MH  - Aged
MH  - *Brassica
MH  - *Diet
MH  - Glutathione Transferase/*genetics/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Prostate/*metabolism
MH  - Prostatic Neoplasms/genetics/*metabolism
MH  - Risk Factors
MH  - *Signal Transduction
PMC - PMC2430620
COIS- Competing Interests: Richard Mithen is a co-inventor on patents (US:6340784 and 
      Europe P1069819B1) associated with high glucosinolate broccoli.
EDAT- 2008/07/04 09:00
MHDA- 2008/10/23 09:00
PMCR- 2008/07/02
CRDT- 2008/07/04 09:00
PHST- 2008/02/20 00:00 [received]
PHST- 2008/05/19 00:00 [accepted]
PHST- 2008/07/04 09:00 [pubmed]
PHST- 2008/10/23 09:00 [medline]
PHST- 2008/07/04 09:00 [entrez]
PHST- 2008/07/02 00:00 [pmc-release]
AID - 08-PONE-CT-03697R1 [pii]
AID - 10.1371/journal.pone.0002568 [doi]
PST - epublish
SO  - PLoS One. 2008 Jul 2;3(7):e2568. doi: 10.1371/journal.pone.0002568.