Cargando…

Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

BACKGROUND: Cruciferous vegetables have been associated with the chemoprevention of cancer. Epigenetic regulators have been identified as important targets for prostate cancer chemoprevention. Treatment of human prostate cancer cells with sulforaphane (SFN), a chemical from broccoli and broccoli spr...

Descripción completa

Detalles Bibliográficos
Autores principales: Beaver, Laura M, Lӧhr, Christiane V, Clarke, John D, Glasser, Sarah T, Watson, Greg W, Wong, Carmen P, Zhang, Zhenzhen, Williams, David E, Dashwood, Roderick H, Shannon, Jackilen, Thuillier, Philippe, Ho, Emily
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041877/
https://www.ncbi.nlm.nih.gov/pubmed/30019025
http://dx.doi.org/10.1093/cdn/nzy002
_version_ 1783339062258565120
author Beaver, Laura M
Lӧhr, Christiane V
Clarke, John D
Glasser, Sarah T
Watson, Greg W
Wong, Carmen P
Zhang, Zhenzhen
Williams, David E
Dashwood, Roderick H
Shannon, Jackilen
Thuillier, Philippe
Ho, Emily
author_facet Beaver, Laura M
Lӧhr, Christiane V
Clarke, John D
Glasser, Sarah T
Watson, Greg W
Wong, Carmen P
Zhang, Zhenzhen
Williams, David E
Dashwood, Roderick H
Shannon, Jackilen
Thuillier, Philippe
Ho, Emily
author_sort Beaver, Laura M
collection PubMed
description BACKGROUND: Cruciferous vegetables have been associated with the chemoprevention of cancer. Epigenetic regulators have been identified as important targets for prostate cancer chemoprevention. Treatment of human prostate cancer cells with sulforaphane (SFN), a chemical from broccoli and broccoli sprouts, inhibits epigenetic regulators such as histone deacetylase (HDAC) enzymes, but it is not known whether consumption of a diet high in broccoli sprouts impacts epigenetic mechanisms in an in vivo model of prostate cancer. OBJECTIVE: In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we tested the hypothesis that a broccoli sprout diet suppresses prostate cancer, inhibits HDAC expression, alters histone modifications, and changes the expression of genes regulated by HDACs. METHODS: TRAMP mice were fed a 15% broccoli sprout or control AIN93G diet; tissue samples were collected at 12 and 28 wk of age. RESULTS: Mice fed broccoli sprouts had detectable amounts of SFN metabolites in liver, kidney, colon, and prostate tissues. Broccoli sprouts reduced prostate cancer incidence and progression to invasive cancer by 11- and 2.4-fold at 12 and 28 wk of age, respectively. There was a significant decline in HDAC3 protein expression in the epithelial cells of prostate ventral and anterior lobes at age 12 wk. Broccoli sprout consumption also decreased histone H3 lysine 9 trimethylation in the ventral lobe (age 12 wk), and decreased histone H3 lysine 18 acetylation in all prostate lobes (age 28 wk). A decline in p16 mRNA levels, a gene regulated by HDAC3, was associated with broccoli sprout consumption, but no significant changes were noted at the protein level. CONCLUSIONS: Broccoli sprout intake was associated with a decline in prostate cancer occurrence and HDAC3 protein expression in the prostate, extending prior work that implicated loss of HDAC3/ corepressor interactions as a key preventive mechanism by SFN in vivo.
format Online
Article
Text
id pubmed-6041877
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-60418772018-07-17 Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice Beaver, Laura M Lӧhr, Christiane V Clarke, John D Glasser, Sarah T Watson, Greg W Wong, Carmen P Zhang, Zhenzhen Williams, David E Dashwood, Roderick H Shannon, Jackilen Thuillier, Philippe Ho, Emily Curr Dev Nutr Original Research BACKGROUND: Cruciferous vegetables have been associated with the chemoprevention of cancer. Epigenetic regulators have been identified as important targets for prostate cancer chemoprevention. Treatment of human prostate cancer cells with sulforaphane (SFN), a chemical from broccoli and broccoli sprouts, inhibits epigenetic regulators such as histone deacetylase (HDAC) enzymes, but it is not known whether consumption of a diet high in broccoli sprouts impacts epigenetic mechanisms in an in vivo model of prostate cancer. OBJECTIVE: In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we tested the hypothesis that a broccoli sprout diet suppresses prostate cancer, inhibits HDAC expression, alters histone modifications, and changes the expression of genes regulated by HDACs. METHODS: TRAMP mice were fed a 15% broccoli sprout or control AIN93G diet; tissue samples were collected at 12 and 28 wk of age. RESULTS: Mice fed broccoli sprouts had detectable amounts of SFN metabolites in liver, kidney, colon, and prostate tissues. Broccoli sprouts reduced prostate cancer incidence and progression to invasive cancer by 11- and 2.4-fold at 12 and 28 wk of age, respectively. There was a significant decline in HDAC3 protein expression in the epithelial cells of prostate ventral and anterior lobes at age 12 wk. Broccoli sprout consumption also decreased histone H3 lysine 9 trimethylation in the ventral lobe (age 12 wk), and decreased histone H3 lysine 18 acetylation in all prostate lobes (age 28 wk). A decline in p16 mRNA levels, a gene regulated by HDAC3, was associated with broccoli sprout consumption, but no significant changes were noted at the protein level. CONCLUSIONS: Broccoli sprout intake was associated with a decline in prostate cancer occurrence and HDAC3 protein expression in the prostate, extending prior work that implicated loss of HDAC3/ corepressor interactions as a key preventive mechanism by SFN in vivo. Oxford University Press 2017-12-26 /pmc/articles/PMC6041877/ /pubmed/30019025 http://dx.doi.org/10.1093/cdn/nzy002 Text en © 2018, Stamm et al. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Beaver, Laura M
Lӧhr, Christiane V
Clarke, John D
Glasser, Sarah T
Watson, Greg W
Wong, Carmen P
Zhang, Zhenzhen
Williams, David E
Dashwood, Roderick H
Shannon, Jackilen
Thuillier, Philippe
Ho, Emily
Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
title Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
title_full Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
title_fullStr Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
title_full_unstemmed Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
title_short Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice
title_sort broccoli sprouts delay prostate cancer formation and decrease prostate cancer severity with a concurrent decrease in hdac3 protein expression in transgenic adenocarcinoma of the mouse prostate (tramp) mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041877/
https://www.ncbi.nlm.nih.gov/pubmed/30019025
http://dx.doi.org/10.1093/cdn/nzy002
work_keys_str_mv AT beaverlauram broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT löhrchristianev broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT clarkejohnd broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT glassersaraht broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT watsongregw broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT wongcarmenp broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT zhangzhenzhen broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT williamsdavide broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT dashwoodroderickh broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT shannonjackilen broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT thuillierphilippe broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice
AT hoemily broccolisproutsdelayprostatecancerformationanddecreaseprostatecancerseveritywithaconcurrentdecreaseinhdac3proteinexpressionintransgenicadenocarcinomaofthemouseprostatetrampmice