Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro
Although 5-fluorouracil (5-FU) is a cornerstone of colorectal cancer (CRC) treatment, its efficacy is often limited by resistance. Wnt/β-catenin signalling plays a crucial role in CRC carcinogenesis and resistance, as Wnt expression is upregulated in 5-FU-resistant cells, protecting them from cell c...
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| Format: | Article |
| Language: | English |
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Elsevier
2025
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| Online Access: | https://repository.londonmet.ac.uk/10088/1/1-s2.0-S2405844025010874-main.pdf |
| _version_ | 1824446530759688192 |
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| author | Smarslik, Maren Inal, Jameel |
| author_facet | Smarslik, Maren Inal, Jameel |
| author_sort | Smarslik, Maren |
| collection | LMU |
| description | Although 5-fluorouracil (5-FU) is a cornerstone of colorectal cancer (CRC) treatment, its efficacy is often limited by resistance. Wnt/β-catenin signalling plays a crucial role in CRC carcinogenesis and resistance, as Wnt expression is upregulated in 5-FU-resistant cells, protecting them from cell cycle arrest and apoptosis, thereby contributing to drug resistance. The small molecule inhibitor β-catenin responsive transcription inhibitor 3 (iCRT3) disrupts Wnt/β-catenin signalling and may enhance CRC sensitivity to 5-FU, overcoming resistance. In this study, the cytotoxic effects of 5-FU and iCRT3 were investigated using the Caco-2 colon adenocarcinoma cell line, marking the first investigation of their combined effects. To this end, the half-maximal inhibitory concentration (IC50) values were determined using the MTT assay. Subsequently, the drugs were combined in different ways, and drug combination index (DCI) calculations were performed to evaluate their interaction. iCRT3 was found to be 2.45-fold more potent than 5-FU (p = 0.1982). Drug combination significantly increased the IC50 compared to 5-FU, with a 40.95-fold increase (p = 0.0022) when 5-FU was fixed (2.56 μM) and a 43.5-fold increase (p = 0.0023) when iCRT3 was fixed (2.41 μM). Two-way ANOVA showed significant impacts from both drug concentration (50.93%) and treatment condition (25.31%) on cell viability (p < 0.0001). DCI analysis confirmed strong synergism with fixed 5-FU (DCI = 0.154) and synergism with fixed iCRT3 (DCI = 0.618), indicating that combining 5-FU and iCRT3 could be a promising strategy for CRC treatment and warranting further investigation. |
| first_indexed | 2025-02-19T01:16:38Z |
| format | Article |
| id | oai:repository.londonmet.ac.uk:10088 |
| institution | London Metropolitan University |
| language | English |
| last_indexed | 2025-02-19T01:16:38Z |
| publishDate | 2025 |
| publisher | Elsevier |
| record_format | eprints |
| spelling | oai:repository.londonmet.ac.uk:100882025-02-17T10:43:55Z https://repository.londonmet.ac.uk/10088/ Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro Smarslik, Maren Inal, Jameel 610 Medicine & health Although 5-fluorouracil (5-FU) is a cornerstone of colorectal cancer (CRC) treatment, its efficacy is often limited by resistance. Wnt/β-catenin signalling plays a crucial role in CRC carcinogenesis and resistance, as Wnt expression is upregulated in 5-FU-resistant cells, protecting them from cell cycle arrest and apoptosis, thereby contributing to drug resistance. The small molecule inhibitor β-catenin responsive transcription inhibitor 3 (iCRT3) disrupts Wnt/β-catenin signalling and may enhance CRC sensitivity to 5-FU, overcoming resistance. In this study, the cytotoxic effects of 5-FU and iCRT3 were investigated using the Caco-2 colon adenocarcinoma cell line, marking the first investigation of their combined effects. To this end, the half-maximal inhibitory concentration (IC50) values were determined using the MTT assay. Subsequently, the drugs were combined in different ways, and drug combination index (DCI) calculations were performed to evaluate their interaction. iCRT3 was found to be 2.45-fold more potent than 5-FU (p = 0.1982). Drug combination significantly increased the IC50 compared to 5-FU, with a 40.95-fold increase (p = 0.0022) when 5-FU was fixed (2.56 μM) and a 43.5-fold increase (p = 0.0023) when iCRT3 was fixed (2.41 μM). Two-way ANOVA showed significant impacts from both drug concentration (50.93%) and treatment condition (25.31%) on cell viability (p < 0.0001). DCI analysis confirmed strong synergism with fixed 5-FU (DCI = 0.154) and synergism with fixed iCRT3 (DCI = 0.618), indicating that combining 5-FU and iCRT3 could be a promising strategy for CRC treatment and warranting further investigation. Elsevier 2025-02-13 Article PeerReviewed text en cc_by_nc_nd_4 https://repository.londonmet.ac.uk/10088/1/1-s2.0-S2405844025010874-main.pdf Smarslik, Maren and Inal, Jameel (2025) Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro. Heliyon (e42706). pp. 1-16. ISSN 24058440 https://doi.org/10.1016/j.heliyon.2025.e42706 10.1016/j.heliyon.2025.e42706 10.1016/j.heliyon.2025.e42706 |
| spellingShingle | 610 Medicine & health Smarslik, Maren Inal, Jameel Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro |
| title | Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro |
| title_full | Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro |
| title_fullStr | Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro |
| title_full_unstemmed | Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro |
| title_short | Synergistic effect of 5-fluorouracil and the small molecule Wnt/β-catenin inhibitor iCRT3 on Caco-2 colorectal cancer cells in vitro |
| title_sort | synergistic effect of 5 fluorouracil and the small molecule wnt β catenin inhibitor icrt3 on caco 2 colorectal cancer cells in vitro |
| topic | 610 Medicine & health |
| url | https://repository.londonmet.ac.uk/10088/1/1-s2.0-S2405844025010874-main.pdf |
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