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Anti-cancer effect and its mechanism of urolithin A: research progress

Published on Feb. 15, 2023Total Views: 1091 times Total Downloads: 447 times Download Mobile

Author: Mi TIAN Li-Rong ZHAO Yu LAN Xian-Xi GUO Ben-Hong ZHOU

Affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China

Keywords: Urolithin A Anti-cancer effect Mechanism

DOI: 10.19960/j.issn.1005-0698.202302012

Reference: Mi TIAN, Li-Rong ZHAO, Yu LAN, Xian-Xi GUO, Ben-Hong ZHOU.Anti-cancer effect and its mechanism of urolithin A: research progress[J].Yaowu Liuxingbingxue Zazhi,2023, 32(2): 213-220.DOI: 10.19960/j.issn.1005-0698.202302012.[Article in Chinese]

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Abstract

Urolithin A is a substance produced by natural medicine ellagitannins after multi-stage metabolism of intestinal flora in vivo. Studies have shown that urolithin A has good anti-cancer activity. In this paper, the anticancer activities of urolithin A against bladder cancer, liver cancer, breast cancer, leukemia, prostate cancer, colorectal cancer and other cancers were reviewed to provide a reference for clinical research of urolithin A as a potential anti-tumor drug.

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References

1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33. DOI: 10.3322/caac.21708.

2. Ma L, Zhang MM, Zhao R, et al. Plant natural products: promising resources for cancer chemopreven-tion[J]. Molecules, 2021, 26(4): 933. DOI: 10.3390/molecules 26040933.

3. Kasimsetty SG, Bialonska D, Reddy MK, et al. Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cells[J]. J Agric Food Chem, 2009, 57(22): 10636-10644. DOI: 10.1021/jf902716r.

4. Sanchez-Gonzalez C, Ciudad CJ, Noe V, et al. Walnut polyphenol metabolites, urolithins A and B, in-hibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells[J]. Food Funct, 2014, 5(11): 2922-2930. DOI: 10.1039/c4fo00542b.

5. Stanislawska IJ, Granica S, Piwowarski JP, et al. The activity of urolithin a and M4 valerolactone, co-lonic microbiota metabolites of polyphenols, in a prostate cancer in vitro model[J]. Planta Med, 2019, 85(2): 118-125. DOI: 10.1055/a-0755-7715.

6. Dahiya NR, Chandrasekaran B, Kolluru V, et al. A natural molecule, urolithin A, downregulates andro-gen receptor activation and suppresses growth of prostate cancer[J]. Mol Carcinog, 2018, 57(10): 1332-1341. DOI: 10.1002/mc.22848.

7. Saleem YIM, Albassam H, Selim M. Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner [J]. Eur J Nut, 2020, 59(4): 1607-1618 . DOI: 10.1007/s00394-019-02016-2.

8. Sanchez-Gonzalez C, Ciudad CJ, Izquierdo-Pulido M, et al. Urolithin A causes p21 up-regulation in prostate cancer cells [J]. Eur J Nutr, 2016, 55(3): 1099-1112. DOI: 10.1007/s00394-015-0924-z.

9. Gonzalez-Sarrias A, Tome-Carneiro J, Bellesia A, et al. The ellagic acid-derived gut microbiota metab-olite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells[J]. Food Funct, 2015, 6(5): 1460-1469. DOI: 10.1039/c5fo00120j.

10.Gonzalez-Sarrias A, Espin JC, Tomas-Barberan FA, et al. Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins[J]. Mol Nutr Food Res, 2009, 53(6): 686-698. DOI: 10.1002/mnfr.200800150.

11.Gonzalez-Sarrias A, Azorin-Ortuno M, Yanez-Gascon MJ, et al. Dissimilar in vitro and in vivo effects of ellagic acid and its microbiota-derived metabolites, urolithins, on the cytochrome P450 1A1[J]. J Agric Food Chem, 2009, 57(12): 5623-5632. DOI: 10.1021/jf900725e.

12.Gonzalez-Sarrias A, Gimenez-Bastida JA, Nunez-Sanchez MA, et al. Phase-II metabolism limits the an-tiproliferative activity of urolithins in human colon cancer cells [J]. Eur J Nutr, 2014, 53(3): 853-864. DOI: 10.1007/s00394-013-0589-4.

13.Gonzalez-Sarrias A, Nunez-Sanchez MA, Garcia-Villalba R, et al. Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism[J]. Eur J Nutr, 2017, 56(2): 831-841. DOI: 10.1007/s00394-013-0589-4.

14.Sharma M, Li LY, Celver J, et al. Effects of fruit ellagitannin extracts, ellagic acid, and their colonic me-tabolite, urolithin A, on wnt signaling[J]. J Agric Food Chem, 2010, 58(7): 3965-3969. DOI: 10.1021/jf902857v.

15.Kasimsetty SG, Bialonska D, Reddy MK, et al. Colon cancer chemopreventive activities of pomegran-ate ellagitannins and urolithins[J]. J Agric Food Chem, 2010, 58(4): 2180-2187. DOI: 10.1021/jf903762h.

16.Cho H, Jung H, Lee H, et al. Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells[J]. Food Funct, 2015, 6(5): 1675-1683. DOI: 10.1039/c5fo00274e.

17.El-Wetidy MS, Ahmad R, Rady I, et al. Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactiveoxygen species production in colorectal cancer cells[J]. Cell Stress & Chaperones, 2021, 26(3): 473-493. DOI: 10.1039/c5fo00274e.

18.Zhao WH, Shi FQ, Guo ZK, et al. Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells[J]. Mol Carcinog, 2018, 57(2): 193-200. DOI: 10.1002/mc.22746.

19.Qiu ZP, Zhou BH, Jin L, et al. In vitro antioxidant and antiproliferative effects of ellagic acid and its co-lonic metabolite, urolithins, on human bladder cancer T24 cells[J]. Food Chem Toxicol, 2013, 59: 428-437. DOI: 10.1016/j.fct.2013.06.025.

20.Liberal J, Carmo A, Gomes C, et al. Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells[J]. Invest New Drugs, 2017, 35(6): 671-681. DOI: 10.1007/s10637-017-0483-7.

21.Alzahrani AM, Mohammed MRS, Alghamdi RA, et al. Urolithin A and B alter cellular metabolism and induce metabolites associated with apoptosis in leukemic cells[J]. Int J Mol Sci, 2021, 22(11): 5465. DOI: 10.3390/ijms22115465.

22.Molina JR, Yang PG, Cassivi SD, et al. Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship[J]. Mayo Clin Proc, 2008, 83(5): 584-594. DOI: 10.4065/83.5.584.

23.Cheng F, Dou JT, Zhang Y, et al. Urolithin A inhibits epithelial-mesenchymal transition in lung cancer cells via p53-mdm2-snail pathway[J]. Onco Targets Ther, 2021, 14: 3199-3208. DOI: 10.2147/OTT.S305595.

24.Chen X, Calvisi DF. Hydrodynamic transfection for generation of novel mouse models for liver cancer research[J]. Am J Pathol, 2014, 184(4): 912-923. DOI: 10.1016/j.ajpath.2013.12.002.

25.Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular car-cinoma[J]. CA Cancer J Clin, 2012, 62(6): 394-399. DOI: 10.3322/caac.21161.

26.Wang Y, Qiu ZP, Zhou BH, et al. In vitro antiproliferative and antioxidant effects of urolithin A, the co-lonic metabolite of ellagic acid, on hepatocellular carcinomas HepG2 cells [J]. Toxicol In Vitro, 2015, 29(5): 1107-1115. DOI: 10.1016/j.tiv.2015.04.008.

27.Qiu ZP, Zhou JX, Zhang C, et al. Antiproliferative effect of urolithin A, the ellagic acid-derived colonic metabolite, on hepatocellular carcinoma HepG2.2.15 cells by targeting Lin28a/let-7a axis[J]. Braz J Med Biol Res, 2018, 51(7) e7220. DOI: 10.1590/1414-431x20187220.

28.Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1): 7-30. DOI: 10.3322/caac.21332

29.Totiger TM, Srinivasan S, Jala VR, et al. Urolithin A, a novel natural compound to target PI3K/AKT/mTOR pathway in pancreatic cancer[J]. Mol Cancer Ther, 2019, 18(2): 301-311. DOI: 10.1158/1535-7163.MCT-18-0464.

30.Zhang W, Chen JH, Aguilera-Barrantes I, et al. Urolithin A suppresses the proliferation of endometrial cancer cells by mediating estrogen receptor-alpha-dependent gene expression[J]. Mol Nutr Food Res, 2016, 60(11): 2387-2395. DOI: 10.1002/mnfr.201600048.

31.Khandekar MJ, Cohen P, Spiegelman BM. Molecular mechanisms of cancer development in obesity [J]. Nat Rev Cancer, 2011, 11(12): 886-895. DOI: 10.1038/nrc3174.

32.Huang YW, Chen JH, Rader JS, et al. Preventive effects by black raspberries of endometrial carcinoma initiation and promotion induced by a high-fat diet[J]. Mol Nutr Food Res, 2019, 63(12): e1900013. DOI: 10.1002/mnfr.201900013.

33.Alauddin M, Okumura T, Rajaxavier J, et al. Gut bacterial metabolite urolithin a decreases actin polymerization and migration in cancer cells[J]. Mol Nutr Food Res, 2020, 64(7): e1900390. DOI: 10.1002/mnfr.201900390.

34.Donepudi MS, Kondapalli K, Amos SJ, et al. Breast cancer statistics and markers [J]. J Cancer Res Ther, 2014, 10(3): 506-511. DOI: 10.4103/0973-1482.137927.

35.Larrosa M, Gonzalez-Sarrias A, Garcia-Conesa MT, et al. Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities[J]. J Agric Food Chem, 2006, 54(5): 1611-1620. DOI: 10.1021/jf0527403.

36.Dellafiora L, Milioli M, Falco A, et al. A hybrid in silico/in vitro target fishing study to mine novel tar-gets of urolithin A and B: a step towards a better comprehension of their estrogenicity[J]. Mol Nutr Food Res, 2020, 64(16): e2000289. DOI: 10.1002/mnfr.202000289.

37.Adams LS, Zhang YJ, Seeram NP, et al. Pomegranate ellagitannin-derived compounds exhibit antipro-liferative and antiaromatase activity in breast cancer cells in vitro[J]. Cancer Prev Res (Phila), 2010, 3(1): 108-113. DOI: 10.1158/1940-6207.CAPR-08-0225.

38.Borst P, Elferink RO. Mammalian ABC transporters in health and disease [J]. Annu Rev Biochem, 2002, 71: 537-592. DOI: 10.1146/annurev.biochem.71.102301.093055.

39.Gonzalez-Sarrias A, Miguel V, Merino G, et al. The gut microbiota ellagic acid-derived metabolite uro-lithin a and its sulfate conjugate are substrates for the drug efflux transporter breast cancer re-sistance protein (ABCG2/BCRP)[J]. J Agric Food Chem, 2013, 61(18): 4352-4359. DOI: 10.1021/jf4007505.

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