ArticleCancer biomarkers : section A of Disease markers2019
Esculetin enhances the inhibitory effect of 5-Fluorouracil on the proliferation, migration and epithelial-mesenchymal transition of colorectal cancer.
Article in Cancer biomarkers : section A of Disease markers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Coumarins in the tumor-immune application: from molecular mechanisms to therapeutic innovations.Frontiers in immunology · 2025Review
- Modulation of hypoxia-inducible factor-1 signaling pathways in cancer angiogenesis, invasion, and metastasis by natural compounds: a comprehensive and critical review.Cancer metastasis reviews · 2024Review
- The possible anti-tumor actions and mechanisms of active metabolites from Cortex Fraxini.Frontiers in pharmacology · 2024Review
- Esculetin unveiled: Decoding its anti-tumor potential through molecular mechanisms-A comprehensive review.Cancer reports (Hoboken, N.J.) · 2024Review
- Antitumor Effects of Esculetin, a Natural Coumarin Derivative, against Canine Mammary Gland Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis.Veterinary sciences · 2023Article
- The interferon regulatory factor 6 promotes cisplatin sensitivity in colorectal cancer.Bioengineered · 2022Article
- Coumarin Derivatives Exert Anti-Lung Cancer Activity by Inhibition of Epithelial-Mesenchymal Transition and Migration in A549 Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Wnt/β‑catenin signaling: Causes and treatment targets of drug resistance in colorectal cancer (Review).Molecular medicine reports · 2021Review
- A Direct and Sensitive Method for Determination of 5-Fluorouracil in Colorectal Cancer Cells: Evaluating the Effect of Stromal Cell on Drug Resistance of Cancer Cells.Journal of analytical methods in chemistry · 2021Article
- Natural Products Targeting the Mitochondria in Cancers.Molecules (Basel, Switzerland) · 2020Review
- Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway.Oxidative medicine and cellular longevity · 2020Review
- Anti-Hepatitis B Virus Activity of Esculetin fromMolecules (Basel, Switzerland) · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is the most common malignant disease worldwide and thus new therapeutic approaches are needed. 5-Fluorouracil (5-FU) remains the most widely used agent to treat colorectal cancer (CRC). However, its clinical efficacy is currently limited by the development of drug resistance. Esculetin (EST), a coumarin, was found to have anti-proliferative and anti-migration activity in cancer.
objectiveThis research aims to evaluated the influence and possible mechanism of EST on the proliferation, migration and epithelial-mesenchymal transition of CRC cell lines. MATERIALS AND
methodsHuman CRC cell lines HT-29, SW480, HCT-116, and Caco-2 were treated with various concentrations of EST (0.2, 2, 20, 200, 2000 μg/ml) or 5-FU (0.1, 1, 10, 100, 1000 μg/ml) for 48 h, and cell viability was determined by the MTT and CCK-8 assay. The motility of HCT-116 cells was detected by scratch assay. Western blot was applied to detect the protein expression. Besides, levels of Wnt3a and VEGF in HCT-116 cell culture medium supernatant were analyzed by ELISA. The anti-tumor effect was detected with HCT-116 subcutaneous tumor bearing tumor model by monitoring the tumor vomume in vivo. Finally, the tumoral expression of VEGF was measured by immunohistochemistry, and the expression of Ki67, PCNA, β-catenin, c-Myc, Cyclin D1, MMP2 and MMP7 was measured by Western blot analysis.
resultsEST inhibited HCT-116 cell proliferation in a dose-dependent manner. Western blot analysis revealed that EST decreased the expression of Ki67, PCNA, N-cadherin, E-cadherin, vimentin, fibronectin, β-catenin, c-Myc, Cyclin D1, MMP2 and MMP7. Furthermore, EST reduced the release of Wnt3a and VEGF into HCT-116 cells culture medium. After EST treatment, the tumor volume was significant smaller than that of the control group, and the tumoral levels of VEGF were decreased. Moreover, western blot analysis indicated that the expression of Ki67, PCNA, β-catenin, c-Myc, Cyclin D1, MMP2 and MMP7 were also significantly decreased after treated with EST. In addition, in vitro and in vivo anti-tumor results demonstrated that EST combined with 5-FU could increase the inhibitory effect of 5-FU on HCT-116 cells proliferation, migration and epithelial-mesenchymal transition.
conclusionsEST enhances the inhibitory effect of 5-FU on the proliferation, migration and epithelial-mesenchymal transition of CRC.
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