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European Journal of Nutrition

Erschienen in:

12.05.2015 | Original Contribution

Urolithin A causes p21 up-regulation in prostate cancer cells

verfasst von: Claudia Sánchez-González, Carlos J. Ciudad, Maria Izquierdo-Pulido, Véronique Noé

Erschienen in: European Journal of Nutrition | Ausgabe 3/2016

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Abstract

Purpose

Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA.

Methods

We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay.

Results

We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment.

Conclusion

Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.

Duthie SJ, Dobson VL (1999) Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. Eur J Nutr 38:28–34CrossRef

Owen RW, Giacosa A, Hull WE et al (2000) The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. Eur J Cancer 36:1235–1247CrossRef

Khan N, Mukhtar H (2013) Modulation of signaling pathways in prostate cancer by green tea polyphenols. Biochem Pharmacol 85:667–672. doi:10.1016/j.bcp.2012.09.027 CrossRef

Corona G, Deiana M, Incani A et al (2007) Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects. Biochem Biophys Res Commun 362:606–611. doi:10.1016/j.bbrc.2007.08.049 CrossRef

Corona G, Deiana M, Incani A et al (2009) Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1. Mol Nutr Food Res 53:897–903. doi:10.1002/mnfr.200800269 CrossRef

Mantena SK, Baliga MS, Katiyar SK (2006) Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells. Carcinogenesis 27:1682–1691. doi:10.1093/carcin/bgl030 CrossRef

Fabiani R, De Bartolomeo A, Rosignoli P et al (2002) Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Eur J Cancer Prev 11:351–358CrossRef

Adams LS, Zhang Y, Seeram NP et al (2010) Pomegranate ellagitannin-derived compounds exhibit anti-proliferative and anti-aromatase activity in breast cancer cells in vitro. Cancer Prev Res (Phila) 3:108–113. doi:10.1158/1940-6207.CAPR-08-0225.Pomegranate CrossRef

Kang NJ, Shin SH, Lee HJ, Lee KW (2011) Polyphenols as small molecular inhibitors of signaling cascades in carcinogenesis. Pharmacol Ther 130:310–324. doi:10.1016/j.pharmthera.2011.02.004 CrossRef

10.

Granci V, Dupertuis YM, Pichard C (2010) Angiogenesis as a potential target of pharmaconutrients in cancer therapy. Curr Opin Clin Nutr Metab Care 13:417–422. doi:10.1097/MCO.0b013e3283392656 CrossRef

11.

Garg AK, Buchholz TA, Aggarwal BB (2005) Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid Redox Signal 7:1630–1647CrossRef

12.

Regueiro J, Sánchez-González C, Vallverdú-Queralt A et al (2014) Comprehensive identification of walnut polyphenols by liquid chromatography coupled to linear ion trap-Orbitrap mass spectrometry. Food Chem 152:340–348. doi:10.1016/j.foodchem.2013.11.158 CrossRef

13.

Cerdá B, Periago P, Espín JC, Tomás-Barberán FA (2005) Identification of urolithin a as a metabolite produced by human colon microflora from ellagic acid and related compounds. J Agric Food Chem 53:5571–5576. doi:10.1021/jf050384i CrossRef

14.

Daniel EM, Kfcjpnick AS, Heur Y et al (1989) Extraction, stability, and quantitation of ellagic acid in various fruits and nuts. J Food Compos Anal 349:338–349CrossRef

15.

Garcia-Muñoz C, Vaillant F (2014) Metabolic fate of ellagitannins: implications for health, and research perspectives for innovative functional foods. Crit Rev Food Sci Nutr 54:1584–1598. doi:10.1080/10408398.2011.644643 CrossRef

16.

Landete JM (2011) Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health. Food Res Int 44:1150–1160. doi:10.1016/j.foodres.2011.04.027 CrossRef

17.

Larrosa M, Tomás-Barberán FA, Espín JC (2006) The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway. J Nutr Biochem 17:611–625. doi:10.1016/j.jnutbio.2005.09.004 CrossRef

18.

Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F (2013) Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evid Based Complement Altern Med 2013:270418. doi:10.1155/2013/270418 CrossRef

19.

Seeram NP, Adams LS, Henning SM et al (2005) In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 16:360–367. doi:10.1016/j.jnutbio.2005.01.006 CrossRef

20.

Vicinanza R, Zhang Y, Henning SM, Heber D (2013) Pomegranate juice metabolites, ellagic acid and urolithin A, synergistically inhibit androgen-independent prostate cancer cell growth via distinct effects on cell cycle control and apoptosis. Evid Based Complement Altern Med 2013:247504. doi:10.1155/2013/247504 CrossRef

21.

Hardman WE, Ion G, Akinsete JA, Witte TR (2011) Dietary walnut suppressed mammary gland tumorigenesis in the C(3)1 TAg mouse. Nutr Cancer 63:960–970. doi:10.1080/01635581.2011.589959 CrossRef

22.

Sánchez-González C, Ciudad CJ, Noé V, Izquierdo-Pulido M (2014) Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells. Food Funct 5:2922–2930. doi:10.1039/c4fo00542b CrossRef

23.

Afman L, Müller M (2006) Nutrigenomics: from molecular nutrition to prevention of disease. J Am Diet Assoc 106:569–576. doi:10.1016/j.jada.2006.01.001 CrossRef

24.

Selga E, Morales C, Noé V et al (2008) Role of caveolin 1, E-cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells. BMC Med Genomics 1:35. doi:10.1186/1755-8794-1-35 CrossRef

25.

Selga E, Oleaga C, Ramírez S et al (2009) Networking of differentially expressed genes in human cancer cells resistant to methotrexate. Genome Med 1:83. doi:10.1186/gm83 CrossRef

26.

Oleaga C, Ciudad CJ, Izquierdo-Pulido M, Noé V (2013) Cocoa flavanol metabolites activate HNF-3β, Sp1, and NFY-mediated transcription of apolipoprotein AI in human cells. Mol Nutr Food Res 57:986–995. doi:10.1002/mnfr.201200507 CrossRef

27.

González-Sarrías A, Giménez-Bastida JA, García-Conesa MT et al (2010) Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice. Mol Nutr Food Res 54:311–322. doi:10.1002/mnfr.200900152 CrossRef

28.

Albrecht M, Jiang W, Kumi-Diaka J et al (2004) Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food 7:274–283. doi:10.1089/1096620041938704 CrossRef

29.

Bell C, Hawthorne S (2008) Ellagic acid, pomegranate and prostate cancer—a mini review. J Pharm Pharmacol 60:139–144. doi:10.1211/jpp.60.2.0001 CrossRef

30.

Malik A, Afaq F, Sarfaraz S et al (2005) Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci 102:14813–14818. doi:10.1073/pnas.0505870102 CrossRef

31.

Seeram NP, Aronson WJ, Zhang Y et al (2007) Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J Agric Food Chem 55:7732–7737. doi:10.1021/jf071303g CrossRef

32.

Espín JC, González-Barrio R, Cerdá B et al (2007) Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans. J Agric Food Chem 55:10476–10485. doi:10.1021/jf0723864 CrossRef

33.

González-Sarrías A, Giménez-Bastida JA, Núñez-Sánchez MA et al (2013) Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. Eur J Nutr. doi:10.1007/s00394-013-0589-4

34.

Dutto I, Tillhon M, Cazzalini O et al (2014) Biology of the cell cycle inhibitor p21(CDKN1A): molecular mechanisms and relevance in chemical toxicology. Arch Toxicol. doi:10.1007/s00204-014-1430-4

35.

Wang LG, Ossowski L, Ferrari AC (2001) Overexpressed androgen receptor linked to p21 WAF1 silencing may be responsible for androgen independence and resistance to apoptosis of a prostate cancer cell line. Cancer Res 61:7544–7551

36.

Piccolo M, Crispi S (2012) The dual role played by p21 may influence the apoptotic or anti-apoptotic fate in cancer. J Can Res Updates 1:189–202

37.

Narayanan BA, Geoffroy O, Willingham MC et al (1999) p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett 136:215–221CrossRef

38.

Zaridze DG (2008) Molecular epidemiology of cancer. Biochemistry 73:532–542. doi:10.1134/S0006297908050064

39.

Alshatwi AA, Hasan TN, Shafi G et al (2012) Validation of the antiproliferative effects of organic extracts from the green husk of Juglans regia L. on PC-3 human prostate cancer cells by assessment of apoptosis-related genes. Evid Based Complement Altern Med 2012:103026. doi:10.1155/2012/103026 CrossRef

40.

Xu H, Yu X, Qu S, Sui D (2013) Juglone, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells. Bioorg Med Chem Lett 23:3631–3634. doi:10.1016/j.bmcl.2013.04.007 CrossRef

41.

Kang MH, Reynolds CP (2009) Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 15:1126–1132. doi:10.1158/1078-0432.CCR-08-0144 CrossRef

42.

Naiki-Ito A, Chewonarin T, Tang M, Pitchakarn P, Kuno T, Ogawa K, Asamoto M, Shirai T, Takahashi S (2015) Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis. Prostate 75:151–160. doi:10.1002/pros.22900 CrossRef

43.

Moroz A, Delella FK, Lacorte LM et al (2013) Fibronectin induces MMP2 expression in human prostate cancer cells. Biochem Biophys Res Commun 430:1319–1321. doi:10.1016/j.bbrc.2012.12.031 CrossRef

Titel: Urolithin A causes p21 up-regulation in prostate cancer cells
verfasst von: Claudia Sánchez-González
Carlos J. Ciudad
Maria Izquierdo-Pulido
Véronique Noé
Publikationsdatum: 12.05.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 3/2016
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-015-0924-z

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Urolithin A causes p21 up-regulation in prostate cancer cells

Abstract

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Results

Conclusion

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