Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer
BackgroundThe natural killer (NK) activity of peripheral blood mononuclear cells (PBMCs) is a crucial defense against the onset and spread of cancer. Studies have shown that patients with reduced NK activity are more susceptible to cancer, and NK activity tends to decrease due to cancer-induced immu...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1503317/full |
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| author | Vladimir Rogovskii Vladimir Rogovskii Vladimir V. Murugin Vladimir V. Murugin Nikolay Vorobyev Nikolay Vorobyev Sergey Popov Nikolay Sturov Alexey Krasheninnikov Alexander Morozov Marina Prokhorova |
| author_facet | Vladimir Rogovskii Vladimir Rogovskii Vladimir V. Murugin Vladimir V. Murugin Nikolay Vorobyev Nikolay Vorobyev Sergey Popov Nikolay Sturov Alexey Krasheninnikov Alexander Morozov Marina Prokhorova |
| author_sort | Vladimir Rogovskii |
| collection | DOAJ |
| description | BackgroundThe natural killer (NK) activity of peripheral blood mononuclear cells (PBMCs) is a crucial defense against the onset and spread of cancer. Studies have shown that patients with reduced NK activity are more susceptible to cancer, and NK activity tends to decrease due to cancer-induced immune suppression. Enhancing the natural cytotoxicity of PBMCs remains a significant task in cancer research.MethodsThis study investigates the potential of urolithin A, a polyphenolic metabolite produced by the gut microbiota, to enhance the natural cytotoxicity of PBMCs in prostate cancer patients and healthy subjects. We investigated the possible role of aryl hydrocarbon receptor (AhR) in this capability of urolithin A. We analyzed the ability of PBMCs preincubated with urolithin A, AhR agonist or antagonist to kill K562 (human chronic myelogenous leukemia) target cells.ResultsOur results demonstrate that urolithin A enhances the natural cytotoxicity of PBMCs in a dose-dependent manner. Specifically, at a concentration of 10 μM, urolithin A increased the NK activity of PBMCs from prostate cancer patients by an average of 23% (95% CI, 7%–38%). In addition, urolithin A modulates the level of cytokine production by PBMCs, decreasing the level of fractalkine, IL-8, and MCP-3. An AhR antagonist (CH223191, 1 μM) also increased NK activity, while an AhR agonist (β-naphthoflavone, 10 μM) did not increase NK activity and partially inhibited the urolithin A-induced enhancement.ConclusionUrolithin A increases the NK activity of PBMCs from patients with prostate cancer and healthy subjects, and the AhR may be involved in this capability of urolithin A. |
| format | Article |
| id | doaj-art-bf33bd948ab141bbb782356cb1f681c7 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-bf33bd948ab141bbb782356cb1f681c72025-01-09T06:10:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15033171503317Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancerVladimir Rogovskii0Vladimir Rogovskii1Vladimir V. Murugin2Vladimir V. Murugin3Nikolay Vorobyev4Nikolay Vorobyev5Sergey Popov6Nikolay Sturov7Alexey Krasheninnikov8Alexander Morozov9Marina Prokhorova10Department of Molecular Pharmacology and Radiobiology, Pirogov Russian National Research Medical University, Moscow, RussiaDepartment of Neuroimmunology, Federal Center of Brain Research and Neurotechnology of the Federal Medical-Biological Agency of Russia, Moscow, RussiaDepartment of Neuroimmunology, Federal Center of Brain Research and Neurotechnology of the Federal Medical-Biological Agency of Russia, Moscow, RussiaLaboratory of Clinical Immunology, National Research Center—Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, RussiaP. Hertsen Moscow Oncology Research Institute, The branch of the FSBI “National Medical Research Radiological Centre” (NMRRC) of the Ministry of Health of the Russian Federation, Moscow, RussiaDepartment of Oncology, Radiotherapy and Reconstructive Surgery of I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, RussiaDepartment of General Practice, Medical Institute, Peoples’ Friendship University of Russia Named After Patrice Lumumba (RUDN University), Moscow, RussiaDepartment of General Practice, Medical Institute, Peoples’ Friendship University of Russia Named After Patrice Lumumba (RUDN University), Moscow, RussiaP. Hertsen Moscow Oncology Research Institute, The branch of the FSBI “National Medical Research Radiological Centre” (NMRRC) of the Ministry of Health of the Russian Federation, Moscow, RussiaP. Hertsen Moscow Oncology Research Institute, The branch of the FSBI “National Medical Research Radiological Centre” (NMRRC) of the Ministry of Health of the Russian Federation, Moscow, RussiaInstitute for Personalized Oncology, Center for Digital Biodesign and Personalized Healthcare, First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Moscow, RussiaBackgroundThe natural killer (NK) activity of peripheral blood mononuclear cells (PBMCs) is a crucial defense against the onset and spread of cancer. Studies have shown that patients with reduced NK activity are more susceptible to cancer, and NK activity tends to decrease due to cancer-induced immune suppression. Enhancing the natural cytotoxicity of PBMCs remains a significant task in cancer research.MethodsThis study investigates the potential of urolithin A, a polyphenolic metabolite produced by the gut microbiota, to enhance the natural cytotoxicity of PBMCs in prostate cancer patients and healthy subjects. We investigated the possible role of aryl hydrocarbon receptor (AhR) in this capability of urolithin A. We analyzed the ability of PBMCs preincubated with urolithin A, AhR agonist or antagonist to kill K562 (human chronic myelogenous leukemia) target cells.ResultsOur results demonstrate that urolithin A enhances the natural cytotoxicity of PBMCs in a dose-dependent manner. Specifically, at a concentration of 10 μM, urolithin A increased the NK activity of PBMCs from prostate cancer patients by an average of 23% (95% CI, 7%–38%). In addition, urolithin A modulates the level of cytokine production by PBMCs, decreasing the level of fractalkine, IL-8, and MCP-3. An AhR antagonist (CH223191, 1 μM) also increased NK activity, while an AhR agonist (β-naphthoflavone, 10 μM) did not increase NK activity and partially inhibited the urolithin A-induced enhancement.ConclusionUrolithin A increases the NK activity of PBMCs from patients with prostate cancer and healthy subjects, and the AhR may be involved in this capability of urolithin A.https://www.frontiersin.org/articles/10.3389/fphar.2024.1503317/fullurolithin Anatural killer activityPBMCsprostate cancercomputational prediction |
| spellingShingle | Vladimir Rogovskii Vladimir Rogovskii Vladimir V. Murugin Vladimir V. Murugin Nikolay Vorobyev Nikolay Vorobyev Sergey Popov Nikolay Sturov Alexey Krasheninnikov Alexander Morozov Marina Prokhorova Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer Frontiers in Pharmacology urolithin A natural killer activity PBMCs prostate cancer computational prediction |
| title | Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer |
| title_full | Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer |
| title_fullStr | Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer |
| title_full_unstemmed | Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer |
| title_short | Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer |
| title_sort | urolithin a increases the natural killer activity of pbmcs in patients with prostate cancer |
| topic | urolithin A natural killer activity PBMCs prostate cancer computational prediction |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1503317/full |
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