ArticleCarcinogenesis2019
Melatonin-mediated downregulation of thymidylate synthase as a novel mechanism for overcoming 5-fluorouracil associated chemoresistance in colorectal cancer cells.
Article in Carcinogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer.Cancer cell international · 2025Review
- Melatonin Overcomes Cancer Multidrug Resistance by Downregulating ABCB1 Expression and Modulating Mitochondrial Function.Journal of pineal research · 2025Article
- Molecular Targets for Pharmacotherapy of Head and Neck Squamous Cell Carcinomas.Current issues in molecular biology · 2025Review
- Melatonin combined with antineoplastic drugs or natural products for cancer treatment: An update.Current research in pharmacology and drug discovery · 2025Review
- An insight into thymidylate synthase inhibitor as anticancer agents: an explicative review.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Molecular functions of microRNAs in colorectal cancer: recent roles in proliferation, angiogenesis, apoptosis, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- The potential therapeutic effect of melatonin in oxaliplatin combination therapy against chemoresistant colorectal cancer cells.Molecular biology reports · 2024Article
- Article
- Unveiling the oncogenic significance of thymidylate synthase in human cancers.American journal of translational research · 2024Article
- scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells.Journal of nanobiotechnology · 2023Article
- Novel strategies to reverse chemoresistance in colorectal cancer.Cancer medicine · 2023Review
- Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.Cell communication and signaling : CCS · 2023Review
- Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer.International journal of molecular sciences · 2022Article
- MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer's disease.Translational neurodegeneration · 2022Article
- A combined treatment with melatonin and andrographis promotes autophagy and anticancer activity in colorectal cancer.Carcinogenesis · 2022Article
- Use of Melatonin in Cancer Treatment: Where Are We?International journal of molecular sciences · 2022Review
- Article
- Visfatin and Resveratrol Differentially Regulate the Expression of Thymidylate Synthase to Control the Sensitivity of Human Colorectal Cancer Cells to Capecitabine Cytotoxicity.Life (Basel, Switzerland) · 2021Article
- Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
background5-Fluorouracil (5-FU) has been established as the first-line chemotherapy for advanced colorectal cancer (CRC); however, acquired chemoresistance is often the cause of poor therapeutic response. Melatonin is a molecule that is associated with circadian rhythms. Although antitumor effects of melatonin have been shown, the underlying mechanism(s) for its activity and its effect, if any, in chemoresistant CRC has not been studied. We aimed to investigate antitumor effects of melatonin, and more specifically its effect on molecular mechanisms in 5-FU resistant CRC cells.
methodsThe cell growth was assessed in CRC cells, patient-derived organoids and 5-FU resistant CRC cells after treatments with melatonin. In addition, the expression of thymidylate synthase (TYMS) and microRNAs (miRNAs) that are targeting TYMS were examined.
resultsWe observed that melatonin inhibited the cell growth in 5-FU resistant CRC cells. In addition, we found that melatonin significantly promoted apoptosis. Furthermore, a combination of melatonin and 5-FU markedly enhanced 5-FU-mediated cytotoxicity in 5-FU resistant cells. In addition, melatonin significantly decreased the expression of TYMS. Interestingly, this effect was manifested through the simultaneous increase in the expression of miR-215-5p, for which, TYMS serves as the direct downstream target for this miRNA.
conclusionsMelatonin facilitates overcoming 5-FU resistance through downregulation of TYMS. Melatonin may serve as a potential therapeutic option on its own, or in conjunction with 5-FU, in the treatment of patients with advanced or chemoresistant CRC.Melatonin inhibits the growth of 5-FU resistant colorectal cancer (CRC) cells through upregulation of miR-215-5p and a concomitant downregulation of TYMS. Melatonin may serve as a potential therapeutic option in the treatment of patients with advanced or chemoresistant CRC.
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