ArticleEuropean journal of nutrition2014
Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells.
Article in European journal of nutrition, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Unveiling the Anticancer Potential of Urolithin A in Colorectal Cancer: A Systematic Review.Oncology research · 2026Pooled it
- Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions.European journal of nutrition · 2021Trial
- Exploring the gut microbiome and metabolomic interactions of antimetabolite drugs to optimize therapy.Gut microbes · 2026Review
- Wheat Bran Stir-Frying Reshapes the Metabolome ofMetabolites · 2026Article
- Microbial Metabolite, Macro Impact: Urolithin A in the Nexus of Insulin Resistance and Colorectal Tumorigenesis.Nutrients · 2025Review
- Emerging evidence of Urolithin A in sports nutrition: bridging preclinical findings to athletic applications.Frontiers in nutrition · 2025Review
- Interplay Between Dietary Phytochemicals and Gut Microbiota in Colorectal Cancer: Future Directions and Considerations.Journal of nutrition and metabolism · 2025Review
- Perspective on the Coevolutionary Role of Host and Gut Microbiota in Polyphenol Health Effects: Metabotypes and Precision Health.Molecular nutrition & food research · 2024Review
- Influence of the gut microbiota on immune cell interactions and cancer treatment.Journal of translational medicine · 2024Review
- The role of gut microbiota and metabolites in cancer chemotherapy.Journal of advanced research · 2024Review
- Mechanistic Insights into the Biological Effects and Antioxidant Activity of Walnut (Antioxidants (Basel, Switzerland) · 2024Review
- Urolithin B inhibits proliferation and migration and promotes apoptosis and necrosis by inducing G2/M arrest and targeting MMP-2/-9 expression in osteosarcoma cells.Journal of biochemical and molecular toxicology · 2023Article
- Effects of Functional and Nutraceutical Foods in the Context of the Mediterranean Diet in Patients Diagnosed with Breast Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Absorption and Metabolism of Urolithin A and Ellagic Acid in Mice and Their Cytotoxicity in Human Colorectal Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Main Determinants Affecting the Antiproliferative Activity of Stilbenes and Their Gut Microbiota Metabolites in Colon Cancer Cells: A Structure-Activity Relationship Study.International journal of molecular sciences · 2022Article
- Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota.Molecular nutrition & food research · 2022Review
- Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review.Current oncology (Toronto, Ont.) · 2022Review
- Polyphenols: Bioavailability, Microbiome Interactions and Cellular Effects on Health in Humans and Animals.Pathogens (Basel, Switzerland) · 2022Review
- Review
- Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUrolithins, gut microbiota metabolites derived from ellagic acid and ellagitannins, reach micromolar concentrations in the colon lumen where can have anti-inflammatory and anticancer effects. The antiproliferative activity of urolithins (Uro-A, Uro-B, Uro-C and Uro-D) and their most relevant in vivo glucuronides were evaluated in three human colon cancer cell lines (Caco-2, SW480 and HT-29).
methodsCell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and Trypan blue exclusion assays. Cell cycle was evaluated by flow cytometry and urolithins metabolism by HPLC–MS/MS.
resultsUrolithins inhibited cell proliferation and cell cycle progression in a time- and dose-dependent manner and arrested the cells at S and G2/M phases, depending on the urolithin. Uro-A exerted the highest antiproliferative activity, followed by Uro-C, Uro-D and Uro-B. Unlike Caco-2 and SW480 cells, HT-29 cells partially overcame the effects after 48 h, which was related to the complete glucuronidation of urolithins. Uro-A or Uro-B glucuronides did not affect cell cycle and showed lower antiproliferative activity than their aglycone counterparts. Uro-A or Uro-B plus inhibitors of drug efflux ABC transporters partially prevented the glucuronidation of urolithins in HT-29 cells which became more sensitive.
conclusionsUro-A, Uro-B, Uro-C and Uro-D exerted different antiproliferative effects depending on the colon cancer cell line. We also report here, for the first time, the role of ABC transporters and Phase-II metabolism in HT-29 cells as a mechanism of cancer resistance against urolithins due to their conversion to glucuronide conjugates that exerted lower antiproliferative activity.
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