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Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells

Stephanie May, Kirsty R. Greenow, Adam T. Higgins, Anna Powell Orcid Logo, Elaine Taylor, Pan Pan, Maria Konstantinou, Colin Nixon, Thomas E. Wooley, Owen J. Sansom, Li‐Shu Wang, Lee Parry Orcid Logo

Molecular Nutrition and Food Research, Volume: 66, Issue: 19, Start page: 2200234

Swansea University Author: Anna Powell Orcid Logo

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DOI (Published version): 10.1002/mnfr.202200234

Abstract

ScopeBlack raspberries (BRBs) have colorectal cancer (CRC) chemo-preventative effects. As CRC originates from an intestinal stem cell (ISC) this study has investigated the impact of BRBs on normal and mutant ISCs.Methods and resultsMice with an inducible Apcfl mutation in either the ISC (Lgr5CreERT2...

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Published in: Molecular Nutrition and Food Research
ISSN: 1613-4125 1613-4133
Published: Wiley 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa61193
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This study uses immunohistochemistry, gene expression analysis, and organoid culture to evaluate the effect of BRBs on intestinal homeostasis. RNAscope is performed for ISC markers on CRC adjacent normal colonic tissue pre and post BRB intervention from patients. 10% BRB diet has no overt effect on murine intestinal homeostasis, despite a reduced stem cell number. Following Apc ISC deletion, BRB diet extends lifespan and reduces tumor area. In the AhCre model, BRB diet attenuates the &#x201C;crypt-progenitor&#x201D; phenotype and reduces ISC marker gene expression. In ex vivo culture BRBs reduce the self-renewal capacity of murine and human Apc deficient organoids. Finally, the study observes a reduction in ISC marker gene expression in adjacent normal crypts following introduction of BRBs to the human bowel.ConclusionBRBs play a role in CRC chemoprevention by protectively regulating the ISC compartment and further supports the use of BRBs in CRC prevention.</abstract><type>Journal Article</type><journal>Molecular Nutrition and Food Research</journal><volume>66</volume><journalNumber>19</journalNumber><paginationStart>2200234</paginationStart><paginationEnd/><publisher>Wiley</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>1613-4125</issnPrint><issnElectronic>1613-4133</issnElectronic><keywords>anthocyanins; black raspberries; chemoprevention; colorectal cancer; intestinal stem cells</keywords><publishedDay>1</publishedDay><publishedMonth>10</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-10-01</publishedDate><doi>10.1002/mnfr.202200234</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>Tenovus Cancer Care. 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spelling 2022-10-06T13:48:11.2361385 v2 61193 2022-09-13 Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells b232c310a6c9458e8669feae92e558a0 0000-0002-8581-5262 Anna Powell Anna Powell true false 2022-09-13 MEDS ScopeBlack raspberries (BRBs) have colorectal cancer (CRC) chemo-preventative effects. As CRC originates from an intestinal stem cell (ISC) this study has investigated the impact of BRBs on normal and mutant ISCs.Methods and resultsMice with an inducible Apcfl mutation in either the ISC (Lgr5CreERT2) or intestinal crypt (AhCre/VillinCreERT2) are fed a control or 10% BRB-supplemented diet. This study uses immunohistochemistry, gene expression analysis, and organoid culture to evaluate the effect of BRBs on intestinal homeostasis. RNAscope is performed for ISC markers on CRC adjacent normal colonic tissue pre and post BRB intervention from patients. 10% BRB diet has no overt effect on murine intestinal homeostasis, despite a reduced stem cell number. Following Apc ISC deletion, BRB diet extends lifespan and reduces tumor area. In the AhCre model, BRB diet attenuates the “crypt-progenitor” phenotype and reduces ISC marker gene expression. In ex vivo culture BRBs reduce the self-renewal capacity of murine and human Apc deficient organoids. Finally, the study observes a reduction in ISC marker gene expression in adjacent normal crypts following introduction of BRBs to the human bowel.ConclusionBRBs play a role in CRC chemoprevention by protectively regulating the ISC compartment and further supports the use of BRBs in CRC prevention. Journal Article Molecular Nutrition and Food Research 66 19 2200234 Wiley 1613-4125 1613-4133 anthocyanins; black raspberries; chemoprevention; colorectal cancer; intestinal stem cells 1 10 2022 2022-10-01 10.1002/mnfr.202200234 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee Tenovus Cancer Care. Grant Number: PhD2013/L25 World Cancer Research Fund. Grant Number: 2013/1006 Cancer Research UK Programme. Grant Numbers: C1295/A15937, A17196 2022-10-06T13:48:11.2361385 2022-09-13T10:08:32.8091875 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Stephanie May 1 Kirsty R. Greenow 2 Adam T. Higgins 3 Anna Powell 0000-0002-8581-5262 4 Elaine Taylor 5 Pan Pan 6 Maria Konstantinou 7 Colin Nixon 8 Thomas E. Wooley 9 Owen J. Sansom 10 Li‐Shu Wang 11 Lee Parry 0000-0002-4467-9196 12 61193__25327__0e008d4c58524e7a9f210cf9878937cb.pdf 61193_VoR.pdf 2022-10-06T13:42:24.9860981 Output 3146569 application/pdf Version of Record true © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
spellingShingle Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
Anna Powell
title_short Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
title_full Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
title_fullStr Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
title_full_unstemmed Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
title_sort Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
author_id_str_mv b232c310a6c9458e8669feae92e558a0
author_id_fullname_str_mv b232c310a6c9458e8669feae92e558a0_***_Anna Powell
author Anna Powell
author2 Stephanie May
Kirsty R. Greenow
Adam T. Higgins
Anna Powell
Elaine Taylor
Pan Pan
Maria Konstantinou
Colin Nixon
Thomas E. Wooley
Owen J. Sansom
Li‐Shu Wang
Lee Parry
format Journal article
container_title Molecular Nutrition and Food Research
container_volume 66
container_issue 19
container_start_page 2200234
publishDate 2022
institution Swansea University
issn 1613-4125
1613-4133
doi_str_mv 10.1002/mnfr.202200234
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description ScopeBlack raspberries (BRBs) have colorectal cancer (CRC) chemo-preventative effects. As CRC originates from an intestinal stem cell (ISC) this study has investigated the impact of BRBs on normal and mutant ISCs.Methods and resultsMice with an inducible Apcfl mutation in either the ISC (Lgr5CreERT2) or intestinal crypt (AhCre/VillinCreERT2) are fed a control or 10% BRB-supplemented diet. This study uses immunohistochemistry, gene expression analysis, and organoid culture to evaluate the effect of BRBs on intestinal homeostasis. RNAscope is performed for ISC markers on CRC adjacent normal colonic tissue pre and post BRB intervention from patients. 10% BRB diet has no overt effect on murine intestinal homeostasis, despite a reduced stem cell number. Following Apc ISC deletion, BRB diet extends lifespan and reduces tumor area. In the AhCre model, BRB diet attenuates the “crypt-progenitor” phenotype and reduces ISC marker gene expression. In ex vivo culture BRBs reduce the self-renewal capacity of murine and human Apc deficient organoids. Finally, the study observes a reduction in ISC marker gene expression in adjacent normal crypts following introduction of BRBs to the human bowel.ConclusionBRBs play a role in CRC chemoprevention by protectively regulating the ISC compartment and further supports the use of BRBs in CRC prevention.
published_date 2022-10-01T08:02:41Z
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