Journal article 494 views 43 downloads
Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells
,
Elaine Taylor,
Pan Pan,
Maria Konstantinou,
Colin Nixon,
Thomas E. Wooley,
Owen J. Sansom,
Li‐Shu Wang,
Lee Parry
Molecular Nutrition and Food Research, Volume: 66, Issue: 19, Start page: 2200234
Swansea University Author:
Anna Powell
-
PDF | Version of Record
© 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License
Download (3MB)
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...
| Published in: | Molecular Nutrition and Food Research |
|---|---|
| ISSN: | 1613-4125 1613-4133 |
| Published: |
Wiley
2022
|
| Online Access: |
Check full text
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa61193 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| 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) 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. |
|---|---|
| Keywords: |
anthocyanins; black raspberries; chemoprevention; colorectal cancer; intestinal stem cells |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Tenovus Cancer Care. Grant Number: PhD2013/L25
World Cancer Research Fund. Grant Number: 2013/1006
Cancer Research UK Programme. Grant Numbers: C1295/A15937, A17196 |
| Issue: |
19 |
| Start Page: |
2200234 |