Journal
BRITISH JOURNAL OF CANCER
Volume 124, Issue 12, Pages 1959-1969Publisher
SPRINGERNATURE
DOI: 10.1038/s41416-021-01354-5
Keywords
-
Categories
Funding
- David Telling Foundation
- Above and Beyond Charitable Trust
- University Hospitals Bristol NHS Foundation Trust
- Medical Research Council Clinical Research Training Fellowship [MR/N001494/1]
- Bowel & Cancer Research
- MRC Research Grant [MR/R017247/1]
- John James Bristol Foundation
- Wellcome Trust [217487/Z/19/Z]
- Bowel Cancer UK [19PT0039]
- Wellcome Trust [217487/Z/19/Z] Funding Source: Wellcome Trust
- Bowel Cancer UK [19PT0039] Funding Source: researchfish
- MRC [MR/R017247/1] Funding Source: UKRI
Ask authors/readers for more resources
The study showed that 5-aminosalicylic acid (5-ASA) inhibited the growth of adenoma cells and suppressed beta-catenin transcriptional activity in vitro. Downregulation of beta-catenin repressed the expression of the stem cell marker LGR5 and suppressed stemness in adenoma and carcinoma cells in 3D models of tumorigenesis.
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, beta-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 beta-catenin transcriptional activity. Downregulation of beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available