Article ; Online: 5-Aminosalicylic acid inhibits stem cell function in human adenoma-derived cells: implications for chemoprophylaxis in colorectal tumorigenesis.
2021 Volume 124, Issue 12, Page(s) 1959–1969
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 ... ...
| 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. |
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| MeSH term(s) | Adenoma/drug therapy ; Adenoma/genetics ; Adenoma/pathology ; Adenoma/prevention & control ; Carcinogenesis/drug effects ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Carcinoma/genetics ; Carcinoma/pathology ; Carcinoma/prevention & control ; Cell Line, Tumor ; Cell Transformation, Neoplastic/drug effects ; Cell Transformation, Neoplastic/genetics ; Chemoprevention/methods ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/genetics ; Colitis, Ulcerative/pathology ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/prevention & control ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mesalamine/pharmacology ; Mesalamine/therapeutic use ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/physiology ; Wnt Signaling Pathway/drug effects ; Wnt Signaling Pathway/genetics | |||||
| Chemical Substances | Mesalamine (4Q81I59GXC) | |||||
| Language | English | |||||
| Publishing date | 2021-03-30 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 80075-2 | |||||
| ISSN | 1532-1827 ; 0007-0920 | |||||
| ISSN (online) | 1532-1827 | |||||
| ISSN | 0007-0920 | |||||
| DOI | 10.1038/s41416-021-01354-5 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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