ArticleFrontiers in oncology2022
Urolithin A targets the AKT/WNK1 axis to induce autophagy and exert anti-tumor effects in cholangiocarcinoma.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026Review
- Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges.Biomedicines · 2025Review
- Autophagy in cholangiocarcinoma: a comprehensive review about roles and regulatory mechanisms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Effect of urolithin A on intracellular survival ofmSphere · 2025Article
- Microbial metabolite-driven immune reprogramming in tumor immunotherapy: mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
- Urolithin A exerts anti-tumor effects on gastric cancer via activating autophagy-Hippo axis and modulating the gut microbiota.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Urolithin C suppresses colorectal cancer progression via the AKT/mTOR pathway.Journal of natural medicines · 2024Article
- Inhibition of WNK Kinases in NK Cells Disrupts Cellular Osmoregulation and Control of Tumor Metastasis.Journal of innate immunity · 2024Article
- Regulatory role of PI3K/Akt/WNK1 signal pathway in mouse model of bone cancer pain.Scientific reports · 2023Article
- Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review.Cureus · 2023Article
- The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut-Brain Axis.Foods (Basel, Switzerland) · 2023Review
- Trapa Bispinosa Roxb. Inhibits the Insulin-Dependent AKT/WNK1 Pathway to Induce Autophagy in Mice with Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urolithin A (UA; 3,8-dihydroxybenzo[c]chromen-6-one), a metabolite generated by intestinal bacteria during the biotransformation of ellagitannins, has gained considerable attention in treating several cancers. Cholangiocarcinoma (CCA) remains one of the most lethal cancers; it grows in a special environment constantly exposed to both blood and bile. Since UA is known to undergo enterohepatic recirculation, we hypothesized that UA might have significant antitumor effects in CCA. Here, we investigated the therapeutic potential of UA in CCA and aimed to elucidate its mechanisms, including autophagy. UA treatment inhibited cell proliferation and induced G2/M phase cell cycle arrest in CCA cells. UA also suppressed cell migration and invasion, but did not cause apoptosis. Furthermore, Western blotting and immunocytochemistry demonstrated increased LC3-II accumulation, while electron microscopy demonstrated induced autophagosomes after UA treatment, suggesting that UA upregulated autophagy in CCA cells. In xenograft mice treated with UA, tumor growth was inhibited with increased LC3-II levels. On the other hand, phospho-kinase array demonstrated downregulation of the AKT/WNK1 pathway. LC3-II expression was elevated in WNK1 knocked down cells, indicating that WNK1 is the key signal for regulating autophagy. Thus, UA exerted antitumor effects by suppressing the AKT/WNK1 signaling pathway and inducing autophagy. In conclusion, UA, a natural, well-tolerated compound, may be a promising therapeutic candidate for advanced CCA.
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