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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Mini-Review Article

Urolithin A 在癌症治疗和预防中的治疗潜力

卷 22, 期 9, 2022

发表于: 28 June, 2022

页: [717 - 724] 页: 8

弟呕挨: 10.2174/1568009622666220602125343

价格: $65

摘要

背景：尿石素 A 是由肠道微生物群产生的天然多酚鞣花酸和鞣花单宁的代谢产物。尿石素 A 在胃肠道中的吸收比其母体物质更好。因此，鞣花单宁含量丰富的食物（如石榴果、核桃、茶等）对人们健康的不同影响可能与个体微生物群含量的差异有关。体内和体外研究表明，尿石素 A 具有多种抗炎和抗癌作用。 目的：在目前的综述中，我们考虑了尿石素 A 的抗炎和直接抗癌作用及其分子机制，这可能是临床试验的基础，估计尿石素 A 的抗癌作用。 结论：尿石素 A 在体外研究中减弱了促炎因子（IL-6、IL-1β、NOS2 等）的产生。口服尿石素 A 治疗在各种体内研究中引起显着的抗癌和抗炎作用，包括结肠炎大鼠模型、角叉菜胶诱导的爪水肿小鼠模型、胰腺癌模型和肥胖模型。这些作用的主要分子机制可能是芳烃受体的调节，其拮抗作用可能导致慢性炎症的减少。尿石素 A 的其他主要目标可能是蛋白质磷酸化过程（例如，它降低蛋白激酶 B 的磷酸化）和 p53 稳定化过程。尿石素 A 的抗炎作用可以在生理相关浓度下达到。这对于预防与癌症慢性炎症相关的免疫抑制可能至关重要。考虑到有利的尿石素 A 安全性，它是一种很有前途的癌症治疗和预防化合物。

关键词: 尿石素 A、多酚、炎症、癌症、AhR 拮抗剂、鞣花单宁。

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[1]
Muku, G.; Murray, I.; Espín, J.; Perdew, G.; Urolithin, A. Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonist. Metabolites, 2018, 8(4), 86.
[http://dx.doi.org/10.3390/metabo8040086] [PMID: 30501068]
[2]
Yang, X.; Tomás-Barberán, F.A. Tea is a significant dietary source of ellagitannins and ellagic acid. J. Agric. Food Chem., 2019, 67(19), 5394-5404.
[http://dx.doi.org/10.1021/acs.jafc.8b05010] [PMID: 30339026]
[3]
Xia, B.; Shi, X.C.; Xie, B.C.; Zhu, M.Q.; Chen, Y.; Chu, X.Y.; Cai, G.H.; Liu, M.; Yang, S.Z.; Mitchell, G.A.; Pang, W.J.; Wu, J.W. Uro-lithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice. PLoS Biol., 2020, 18(3), e3000688.
[http://dx.doi.org/10.1371/journal.pbio.3000688] [PMID: 32218572]
[4]
Ghosh, N.; Das, A.; Biswas, N.; Gnyawali, S.; Singh, K.; Gorain, M.; Polcyn, C.; Khanna, S.; Roy, S.; Sen, C.K. Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD+ and SIRT1. Sci. Rep., 2020, 10(1), 20184.
[http://dx.doi.org/10.1038/s41598-020-76564-7] [PMID: 33214614]
[5]
Al-Harbi, S.A.; Abdulrahman, A.O.; Zamzami, M.A.; Khan, M.I. Urolithins: The gut based polyphenol metabolites of ellagitannins in cancer prevention, a review. Front. Nutr., 2021, 8, 647582.
[http://dx.doi.org/10.3389/fnut.2021.647582] [PMID: 34164422]
[6]
Giménez-Bastida, J.A.; Ávila-Gálvez, M.Á.; Espín, J.C.; González-Sarrías, A. The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells. Food Chem. Toxicol., 2020, 139, 111260.
[http://dx.doi.org/10.1016/j.fct.2020.111260] [PMID: 32179165]
[7]
Okumura, T. The potential as new treatment agent of Urolithin-A metabolized from ellagic acid by gut microbiota in cancer., 2021, 67(2), 131-139.
[8]
Rønning, S.B.; Voldvik, V.; Bergum, S.K.; Aaby, K.; Borge, G.I.A. Ellagic acid and urolithin A modulate the immune response in LPS-stimulated U937 monocytic cells and THP-1 differentiated macrophages. Food Funct., 2020, 11(9), 7946-7959.
[http://dx.doi.org/10.1039/C9FO03008E] [PMID: 32832941]
[9]
Toney, A.M.; Fox, D.; Chaidez, V.; Ramer-Tait, A.E.; Chung, S. Immunomodulatory role of urolithin a on metabolic diseases. Biomedicines, 2021, 9(2), 192.
[http://dx.doi.org/10.3390/biomedicines9020192] [PMID: 33671880]
[10]
Abdelazeem, K.N.M.; Kalo, M.Z.; Beer-Hammer, S.; Lang, F. The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs. Sci. Rep., 2021, 11(1), 7117.
[http://dx.doi.org/10.1038/s41598-021-86514-6] [PMID: 33782464]
[11]
Rogovskii, V. Immune tolerance as the physiologic counterpart of chronic inflammation. Front. Immunol., 2020, 11, 2061.
[http://dx.doi.org/10.3389/fimmu.2020.02061] [PMID: 33117330]
[12]
Rogovskii, V.S. The linkage between inflammation and immune tolerance: Interfering with inflammation in cancer. Curr. Cancer Drug Targets, 2017, 17(4), 325-332.
[http://dx.doi.org/10.2174/1568009617666170109110816] [PMID: 28067176]
[13]
Setrerrahmane, S.; Xu, H. Tumor-related interleukins: Old validated targets for new anti-cancer drug development. Mol. Cancer, 2017, 16(1), 153.
[http://dx.doi.org/10.1186/s12943-017-0721-9] [PMID: 28927416]
[14]
Rogovskii, V. Modulation of inflammation-induced tolerance in cancer. Front. Immunol., 2020, 11, 1180.
[http://dx.doi.org/10.3389/fimmu.2020.01180] [PMID: 32676076]
[15]
Totiger, T.M.; Srinivasan, S.; Jala, V.R.; Lamichhane, P.; Dosch, A.R.; Gaidarski, A.A., III; Joshi, C.; Rangappa, S.; Castellanos, J.; Vemu-la, P.K.; Chen, X.; Kwon, D.; Kashikar, N.; VanSaun, M.; Merchant, N.B.; Nagathihalli, N.S. Urolithin A, a novel natural compound to tar-get PI3K/AKT/mTOR pathway in pancreatic cancer. Mol. Cancer Ther., 2019, 18(2), 301-311.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0464] [PMID: 30404927]
[16]
Bobowska, A.; Granica, S.; Filipek, A.; Melzig, M.F.; Moeslinger, T.; Zentek, J.; Kruk, A.; Piwowarski, J.P. Comparative studies of uro-lithins and their phase II metabolites on macrophage and neutrophil functions. Eur. J. Nutr., 2021, 60(4), 1957-1972.
[http://dx.doi.org/10.1007/s00394-020-02386-y] [PMID: 32960290]
[17]
Wang, Y.; Qiu, Z.; Zhou, B.; Liu, C.; Ruan, J.; Yan, Q.; Liao, J.; Zhu, F. In vitro antiproliferative and antioxidant effects of urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinomas HepG2 cells. Toxicol. In Vitro, 2015, 29(5), 1107-1115.
[http://dx.doi.org/10.1016/j.tiv.2015.04.008] [PMID: 25910917]
[18]
Giridharan, S.; Srinivasan, M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. J. Inflamm. Res., 2018, 11, 407-419.
[http://dx.doi.org/10.2147/JIR.S140188] [PMID: 30464573]
[19]
Komatsu, W.; Kishi, H.; Yagasaki, K.; Ohhira, S. Urolithin A attenuates pro-inflammatory mediator production by suppressing PI3-K/Akt/NF-κB and JNK/AP-1 signaling pathways in lipopolysaccharide-stimulated RAW264 macrophages: Possible involvement of NADPH oxidase-derived reactive oxygen species. Eur. J. Pharmacol., 2018, 833, 411-424.
[http://dx.doi.org/10.1016/j.ejphar.2018.06.023] [PMID: 29932926]
[20]
Rogovskii, V.S.; Popov, S.V.; Sturov, N.V.; Shimanovskii, N.L. The possibility of preventive and therapeutic use of green tea catechins in prostate cancer. Anticancer. Agents Med. Chem., 2019, 19(10), 1223-1231.
[http://dx.doi.org/10.2174/1871520619666190404153058] [PMID: 30947675]
[21]
Zhang, H.Y.; Chen, L.L.; Li, X.J.; Zhang, J. Evolutionary inspirations for drug discovery. Trends Pharmacol. Sci., 2010, 31(10), 443-448.
[http://dx.doi.org/10.1016/j.tips.2010.07.003] [PMID: 20724009]
[22]
Leláková, V.; Šmejkal, K.; Jakubczyk, K.; Veselý, O.; Landa, P.; Václavík, J. Bobáľ P.; Pížová, H.; Temml, V.; Steinacher, T.; Schuster, D.; Granica, S.; Hanáková, Z.; Hošek, J. Parallel in vitro and in silico investigations into anti-inflammatory effects of non-prenylated stil-benoids. Food Chem., 2019, 285, 431-440.
[http://dx.doi.org/10.1016/j.foodchem.2019.01.128] [PMID: 30797367]
[23]
Avgerinos, K.I.; Spyrou, N.; Mantzoros, C.S.; Dalamaga, M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism, 2019, 92, 121-135.
[http://dx.doi.org/10.1016/j.metabol.2018.11.001] [PMID: 30445141]
[24]
Deng, T.; Lyon, C.J.; Bergin, S.; Caligiuri, M.A.; Hsueh, W.A. Obesity, inflammation, and cancer. Annu. Rev. Pathol., 2016, 11(1), 421-449.
[http://dx.doi.org/10.1146/annurev-pathol-012615-044359] [PMID: 27193454]
[25]
Venkateswaran, N.; Conacci-Sorrell, M. Kynurenine: An oncometabolite in colon cancer. Cell Stress, 2020, 4(1), 24-26.
[http://dx.doi.org/10.15698/cst2020.01.210] [PMID: 31922097]
[26]
Zhang, S.; Al-Maghout, T.; Cao, H.; Pelzl, L.; Salker, M.S.; Veldhoen, M.; Cheng, A.; Lang, F.; Singh, Y. Gut bacterial metabolite Urolithin A (UA) mitigates Ca2+ entry in T cells by regulating miR-10a-5p. Front. Immunol., 2019, 10, 1737.
[http://dx.doi.org/10.3389/fimmu.2019.01737] [PMID: 31417547]
[27]
Cheng, F.; Dou, J.; Zhang, Y.; Wang, X.; Wei, H.; Zhang, Z.; Cao, Y.; Wu, Z.; Urolithin, A. Urolithin a inhibits epithelial–mesenchymal transition in lung cancer cells via P53-Mdm2-Snail pathway. OncoTargets Ther., 2021, 14, 3199-3208.
[http://dx.doi.org/10.2147/OTT.S305595] [PMID: 34040386]
[28]
Ahsan, A.; Zheng, Y.R.; Wu, X.L.; Tang, W.D.; Liu, M.R.; Ma, S.J.; Jiang, L.; Hu, W.W.; Zhang, X.N.; Chen, Z. Urolithin A- activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo. CNS Neurosci. Ther., 2019, 25(9), 976-986.
[http://dx.doi.org/10.1111/cns.13136] [PMID: 30972969]
[29]
Zhao, W.; Shi, F.; Guo, Z.; Zhao, J.; Song, X.; Yang, H. Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells. Mol. Carcinog., 2018, 57(2), 193-200.
[http://dx.doi.org/10.1002/mc.22746] [PMID: 28976622]
[30]
Singh, A.; D’Amico, D.; Andreux, P.A.; Dunngalvin, G.; Kern, T.; Blanco-Bose, W.; Auwerx, J.; Aebischer, P.; Rinsch, C. Direct supple-mentation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve con-sistent levels across the population. Eur. J. Clin. Nutr., 2022, 76(2), 297-308.
[PMID: 34117375]
[31]
Smith, B.N.; Burton, L.J.; Henderson, V.; Randle, D.D.; Morton, D.J.; Smith, B.A.; Taliaferro-Smith, L.; Nagappan, P.; Yates, C.; Zayzafoon, M.; Chung, L.W.K.; Odero-Marah, V.A. Snail promotes epithelial mesenchymal transition in breast cancer cells in part via ac-tivation of nuclear ERK2. PLoS One, 2014, 9(8), e104987.
[http://dx.doi.org/10.1371/journal.pone.0104987] [PMID: 25122124]
[32]
Norden, E.; Heiss, E.H. Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells. Carcinogenesis, 2019, 40(1), 93-101.
[http://dx.doi.org/10.1093/carcin/bgy158] [PMID: 30418550]
[33]
Sánchez-González, C.; Ciudad, C.J.; Izquierdo-Pulido, M.; Noé, V. Urolithin A causes p21 up-regulation in prostate cancer cells. Eur. J. Nutr., 2016, 55(3), 1099-1112.
[http://dx.doi.org/10.1007/s00394-015-0924-z] [PMID: 25962506]
[34]
Alauddin, M.; Okumura, T.; Rajaxavier, J.; Khozooei, S.; Pöschel, S.; Takeda, S.; Singh, Y.; Brucker, S.Y.; Wallwiener, D.; Koch, A.; Salk-er, M.S. Gut bacterial metabolite urolithin a decreases actin polymerization and migration in cancer cells. Mol. Nutr. Food Res., 2020, 64(7), 1900390.
[http://dx.doi.org/10.1002/mnfr.201900390] [PMID: 31976617]
[35]
El-Wetidy, M.S.; Ahmad, R.; Rady, I.; Helal, H.; Rady, M.I.; Vaali-Mohammed, M.A.; Al-Khayal, K.; Traiki, T.B.; Abdulla, M.H. Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colo-rectal cancer cells. Cell Stress Chaperones, 2021, 26(3), 473-493.
[http://dx.doi.org/10.1007/s12192-020-01189-8] [PMID: 33666815]
[36]
Alzahrani, A.M.; Shait Mohammed, M.R.; Alghamdi, R.A.; Ahmad, A.; Zamzami, M.A.; Choudhry, H.; Khan, M.I. Urolithin A and B alter cellular metabolism and induce metabolites associated with apoptosis in leukemic cells. Int. J. Mol. Sci., 2021, 22(11), 5465.
[http://dx.doi.org/10.3390/ijms22115465] [PMID: 34067305]
[37]
Xue, P.; Fu, J.; Zhou, Y. The Aryl hydrocarbon receptor and tumor immunity. Front. Immunol., 2018, 9, 286.
[http://dx.doi.org/10.3389/fimmu.2018.00286] [PMID: 29487603]
[38]
Zhan, T.; Rindtorff, N.; Boutros, M. Wnt signaling in cancer. Oncogene, 2017, 36(11), 1461-1473.
[http://dx.doi.org/10.1038/onc.2016.304] [PMID: 27617575]
[39]
Zhang, W.; Chen, J.H.; Aguilera-Barrantes, I.; Shiau, C.W.; Sheng, X.; Wang, L.S.; Stoner, G.D.; Huang, Y.W. Urolithin A suppresses the proliferation of endometrial cancer cells by mediating estrogen receptor-α-dependent gene expression. Mol. Nutr. Food Res., 2016, 60(11), 2387-2395.
[http://dx.doi.org/10.1002/mnfr.201600048] [PMID: 27342949]
[40]
Fedotcheva, T.A.; Fedotcheva, N.I.; Shimanovsky, N.L. Progestins as anticancer drugs and chemosensitizers, new targets and applications. Pharmaceutics, 2021, 13(10), 1616.
[http://dx.doi.org/10.3390/pharmaceutics13101616] [PMID: 34683909]
[41]
Heilman, J.; Andreux, P.; Tran, N.; Rinsch, .C Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid Food Chem. Toxicol, 2017, 108(Pt A), pp. 289-297.
[42]
Andreux, P.A.; Blanco-Bose, W.; Ryu, D.; Burdet, F.; Ibberson, M.; Aebischer, P.; Auwerx, J.; Singh, A.; Rinsch, C. The mitophagy activa-tor urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat. Metab., 2019, 1(6), 595-603.
[http://dx.doi.org/10.1038/s42255-019-0073-4] [PMID: 32694802]
[43]
Espín, J.C.; Larrosa, M.; García-Conesa, M.T.; Tomás-Barberán, F. Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: The evidence so far. Evid. Based Complement. Alternat. Med., 2013, 2013, 1-15.
[http://dx.doi.org/10.1155/2013/270418] [PMID: 23781257]
[44]
Giménez-Bastida, J.A.; González-Sarrías, A.; Larrosa, M.; Tomás-Barberán, F.; Espín, J.C.; García-Conesa, M.T. Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells. Mol. Nutr. Food Res., 2012, 56(5), 784-796.
[http://dx.doi.org/10.1002/mnfr.201100677] [PMID: 22648625]
[45]
González-Sarrías, A.; Giménez-Bastida, J.A.; Núñez-Sánchez, M.Á.; Larrosa, M.; García-Conesa, M.T.; Tomás-Barberán, F.A.; Espín, J.C. Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. Eur. J. Nutr., 2014, 53(3), 853-864.
[http://dx.doi.org/10.1007/s00394-013-0589-4] [PMID: 24077694]
[46]
Ávila-Gálvez, M.Á.; Espín, J.C.; González-Sarrías, A. Physiological relevance of the antiproliferative and estrogenic effects of dietary polyphenol aglycones versus their phase-II metabolites on breast cancer cells: A call of caution. J. Agric. Food Chem., 2018, 66(32), 8547-8555.
[http://dx.doi.org/10.1021/acs.jafc.8b03100] [PMID: 30025453]
[47]
Ávila-Gálvez, M.A.; Giménez-Bastida, J.A.; González-Sarrías, A.; Espín, J.C. Tissue deconjugation of urolithin A glucuronide to free uro-lithin A in systemic inflammation. Food Funct., 2019, 10(6), 3135-3141.
[http://dx.doi.org/10.1039/C9FO00298G] [PMID: 31041969]
[48]
Larrosa, M.; González-Sarrías, A.; Yáñez-Gascón, M.J.; Selma, M.V.; Azorín-Ortuño, M.; Toti, S.; Tomás-Barberán, F.; Dolara, P.; Espín, J.C. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon in-flammation on phenolic metabolism. J. Nutr. Biochem., 2010, 21(8), 717-725.
[http://dx.doi.org/10.1016/j.jnutbio.2009.04.012] [PMID: 19616930]
[49]
Singh, R.; Chandrashekharappa, S.; Bodduluri, S.R.; Baby, B.V.; Hegde, B.; Kotla, N.G.; Hiwale, A.A.; Saiyed, T.; Patel, P.; Vijay-Kumar, M.; Langille, M.G.I.; Douglas, G.M.; Cheng, X.; Rouchka, E.C.; Waigel, S.J.; Dryden, G.W.; Alatassi, H.; Zhang, H.G.; Haribabu, B.; Vemula, P.K.; Jala, V.R. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat. Commun., 2019, 10(1), 89.
[http://dx.doi.org/10.1038/s41467-018-07859-7] [PMID: 30626868]
[50]
Ishimoto, H.; Shibata, M.; Myojin, Y.; Ito, H.; Sugimoto, Y.; Tai, A.; Hatano, T. In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A. Bioorg. Med. Chem. Lett., 2011, 21(19), 5901-5904.
[http://dx.doi.org/10.1016/j.bmcl.2011.07.086] [PMID: 21843938]
[51]
Nair, A.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm., 2016, 7(2), 27-31.
[http://dx.doi.org/10.4103/0976-0105.177703] [PMID: 27057123]
[52]
Nagathihalli, N.S.; Castellanos, J.A.; Shi, C.; Beesetty, Y.; Reyzer, M.L.; Caprioli, R.; Chen, X.; Walsh, A.J.; Skala, M.C.; Moses, H.L.; Merchant, N.B. Signal transducer and activator of transcription 3, Mediated remodeling of the tumor microenvironment results in en-hanced tumor drug delivery in a mouse model of pancreatic cancer. Gastroenterology, 2015, 149(7), 1932-1943.e9.
[http://dx.doi.org/10.1053/j.gastro.2015.07.058] [PMID: 26255562]

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