5-aminosalicylic acid inhibits stem cell function in human adenoma derived cells: implications for chemoprophylaxis in colorectal tumorigenesis

Steven W Dixon, Tracey J Collard, Eleanor M H Mortensson, Danny N Legge, Adam Christian Chambers, Alexander Greenhough, Tom J Creed, Ann C Williams*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
36 Downloads (Pure)

Abstract

Background
Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Polyp resection prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing identification of high-risk individuals who may benefit from effective chemoprophylaxis. We aimed to investigate the potential of 5-aminosalicylic acid (5-ASA), a medication used in the treatment of ulcerative colitis, as a possible preventative agent for sporadic CRC.

Methods
Human colorectal adenoma (PC/AA/C1, S/AN/C1 and S/RG/C2), transformed adenoma PC/AA/C1/SB10 and carcinoma cell lines (LS174T and SW620) were treated with 5-ASA. The effect on growth in two- and three-dimensional (3D) culture, β-catenin transcriptional activity and on cancer stemness properties of the cells were investigated.

Results
5-ASA was shown, in vitro, to inhibit the growth of adenoma cells and suppress β-catenin transcriptional activity. Downregulation of β-catenin was found to repress expression of stem cell marker LGR5 (leucine-rich G protein-coupled receptor-5) and functionally suppress stemness in human adenoma and carcinoma cells using 3D models of tumorigenesis.

Conclusions
5-ASA can suppress the cancer stem phenotype in adenoma-derived cells. Affordable and well-tolerated, 5-ASA is an outstanding candidate as a chemoprophylactic medication to reduce the risk of colorectal polyps and CRC in those at high risk.
Original languageEnglish
Pages (from-to)1959-1969
Number of pages11
JournalBritish Journal of Cancer
Volume124
Issue number12
Early online date30 Mar 2021
DOIs
Publication statusPublished - 8 Jun 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • 5-aminosalicylic acid (5-ASA)
  • colorectal cancer
  • β-catenin
  • LGR5

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