Review ArticleReview

Research progress on the anticarcinogenic actions and mechanisms of ellagic acid

Hong-Mei Zhang, Lei Zhao, Hao Li, Hao Xu, Wen-Wen Chen and Lin Tao
Cancer Biology & Medicine June 2014, 11 (2) 92-100; DOI: https://doi.org/10.7497/j.issn.2095-3941.2014.02.004

References

  1. 1.↵
    2. Boyle P,
    3. Levin B. eds.
    World Cancer Report 2008. International Agency for Research on Cancer, 1–260.
  2. 2.↵
  3. 3.↵
    2. Ramasamy S,
    3. Abdul Wahab N,
    4. Zainal Abidin N,
    5. Manickam S,
    6. Zakaria Z.
    Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction. PLoS One 2012;7:e34793.
  4. 4.↵
    2. Cragg GM,
    3. Newman DJ.
    Plants as a source of anti-cancer agents. J Ethnopharmacol 2005;100:72–79.
    OpenUrlCrossRefPubMedWeb of Science
  5. 5.↵
    2. Girish C,
    3. Pradhan SC.
    Drug development for liver diseases: focus on picroliv, ellagic acid and curcumin. Fundam Clin Pharmacol 2008;22:623–632.
    OpenUrlPubMed
  6. 6.
    2. Williner MR,
    3. Pirovani ME,
    4. Güemes DR.
    Ellagic acid content in strawberries of different cultivars and ripening stages. J Sci Food Agric 2003;83:842–845.
    OpenUrlCrossRef
  7. 7.
    2. Bakkalbaşi E,
    3. Menteş O,
    4. Artik N.
    Food ellagitannins-occurrence, effects of processing and storage. Crit Rev Food Sci Nutr 2009;49:283–298.
    OpenUrlPubMed
  8. 8.
    2. Daniel EM,
    3. Krupnick AS,
    4. Heur YH,
    5. Blinzler JA,
    6. Nims RW,
    7. Stoner GD.
    Extraction, stability and, quantitation of ellagic acid in various fruits and nuts. J Food Compost Anal 1989;2:338–349.
    OpenUrl
  9. 9.
    2. Häkkinen S,
    3. Heinonen M,
    4. Kärenlampi S,
    5. Mykkänen H,
    6. Ruuskanen J,
    7. Törrönen R.
    Screening of selected flavanoids and phenolic acids in 19 berries. Food Research International 1999;32:345–353.
    OpenUrlCrossRef
  10. 10.
    2. Atkinson CJ,
    3. Dodds PA,
    4. Ford YY,
    5. Le Mière J,
    6. Taylor JM,
    7. Blake PS, et al.
    Effects of cultivar, fruit number and reflected photosynthetically active radiation on Fragaria x ananassa productivity and fruit ellagic acid and ascorbic acid concentrations. Ann Bot 2006;97:429–441.
    OpenUrlCrossRefPubMed
  11. 11.
    2. Sajid ZI,
    3. Anwar F,
    4. Shabir G,
    5. Rasul G,
    6. Alkharfy KM,
    7. Gilani AH.
    Antioxidant, antimicrobial properties and phenolics of different solvent extracts from bark, leaves and seeds of Pongamia pinnata (L.) Pierre. Molecules 2012;17:3917–3932.
    OpenUrlPubMed
  12. 12.
    2. Wu QY,
    3. Zhou Y,
    4. Jin X,
    5. Guan Y,
    6. Xu M,
    7. Liu LF.
    Chromatographic fingerprint and the simultaneous determination of five bioactive components of geranium carolinianum L. water extract by high performance liquid chromatography. Int J Mol Sci 2011;12:8740–8749.
    OpenUrlPubMed
  13. 13.
    2. Lee, JH,
    3. Johnson JV,
    4. Talcott ST.
    Identification of ellagic acid conjugates and other polyphenolics in muscadine grapes by HPLC-ESI-MS. Journal of Agricultural and Food Chemistry 2005;53:6003–6010.
    OpenUrlCrossRefPubMedWeb of Science
  14. 14.↵
    2. Heber D.
    Multitargeted therapy of cancer by ellagitannins. Cancer Letters 2008;269:262–268.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    2. Wang N,
    3. Wang ZY,
    4. Mo SL,
    5. Loo TY,
    6. Wang DM,
    7. Luo HB, et al.
    Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. Breast Cancer Res Treat 2012;134:943–955.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    2. Vanella L,
    3. Di Giacomo C,
    4. Acquaviva R,
    5. Barbagallo I,
    6. Cardile V,
    7. Kim DH, et al.
    Apoptotic markers in a prostate cancer cell line: Effect of ellagic acid. Oncol Rep 2013;30:2804–2810.
    OpenUrl
  17. 17.↵
    2. Han DH,
    3. Lee MJ,
    4. Kim JH.
    Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer research 2006;26:3601–3606.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    2. Edderkaoui M,
    3. Odinokova I,
    4. Ohno I,
    5. Gukovsky I,
    6. Go VL,
    7. Pandol SJ, et al.
    Ellagic acid induces apoptosis through inhibition of nuclear factor kappa B in pancreatic cancer cells. World J Gastroenterol 2008;14:3672–3680.
    OpenUrlPubMed
  19. 19.↵
    2. Edderkaoui M,
    3. Lugea A,
    4. Hui H,
    5. Eibl G,
    6. Lu QY,
    7. Moro A, et al.
    Ellagic Acid and Embelin Affect Key Cellular Components of Pancreatic Adenocarcinoma, Cancer, and Stellate Cells. Nutr Cancer 2013;65:1232–1244.
    OpenUrl
  20. 20.↵
    2. Zhao M,
    3. Tang SN,
    4. Marsh JL,
    5. Shankar S,
    6. Srivastava RK.
    Ellagic acid inhibits human pancreatic cancer growth in Balb/C nude mice. Cancer Lett 2013;337:210–217.
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    2. Chung YC,
    3. Lu LC,
    4. Tsai MH,
    5. Chen YJ,
    6. Chen YY,
    7. Yao SP, et al.
    The inhibitory effect of ellagic Acid on cell growth of ovarian carcinoma cells. Evid Based Complement Alternat Med 2013;2013:306705.
    OpenUrlPubMed
  22. 22.↵
    2. Huang ST,
    3. Wang CY,
    4. Yang RC,
    5. Chu CJ,
    6. Wu HT,
    7. Pang JH.
    Phyllanthus urinaria Increases Apoptosis and Reduces Telomerase Activity in Human Nasopharyngeal Carcinoma Cells. Forsch Komplementmed 2009;16:34–40.
    OpenUrlPubMed
  23. 23.↵
    2. Mishra S,
    3. Vinayak M.
    Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway. Mol Biol Rep 2013;40:1417–1428.
    OpenUrl
  24. 24.↵
    2. Mishra S,
    3. Vinayak M.
    Ellagic Acid Induces Novel and Atypical PKC Isoforms and Promotes Caspase-3 Dependent Apoptosis by Blocking Energy Metabolism. Nutr Cancer 2014;66:675–681.
    OpenUrl
  25. 25.↵
    2. Aiyer HS,
    3. Warri AM,
    4. Wood DR E,
    5. Hilakivi-Clarke L,
    6. Clarke R.
    Influence of Berry Polyphenols on Receptor Signaling and Cell-Death Pathways: Implications for Breast Cancer Prevention. J Agric Food Chem 2012;60:5693–5708.
    OpenUrlCrossRefWeb of Science
  26. 26.↵
    2. Aiyer HS,
    3. Gupta RC.
    Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of estrogen metabolism. Cancer Prev Res (Phila) 2010;3:727–737.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    2. Aqil F,
    3. Gupta A,
    4. Munagala R,
    5. Jeyabalan J,
    6. Kausar H,
    7. Sharma RJ, et al.
    Antioxidant and antiproliferative activities of anthocyanin/ellagitannin-enriched extracts from Syzygium cumini L. Nutr Cancer 2012;64:428–438.
    OpenUrlCrossRefPubMed
  28. 28.↵
    2. Priyadarsini KI,
    3. Khopde SM,
    4. Kumar SS,
    5. Mohan H.
    Free radical studies of ellagic acid, a natural phenolic antioxidant. J Agric Food Chem 2002;50:2200–2206.
    OpenUrlPubMed
  29. 29.↵
    2. Gerhäuser C,
    3. Klimo K,
    4. Heiss E,
    5. Neumann I,
    6. Gamal-Eldeen A,
    7. Knauft J, et al.
    Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat Res 2003;523–524:163-172.
  30. 30.↵
    2. Spencer WA,
    3. Jeyabalan J,
    4. Kichambre S,
    5. Gupta RC.
    Oxidatively Generated DNA Damage Following Cu(II)-Catalysis of Dopamine and Related Catecholamine Neurotransmitters and Neurotoxins: Role of Reactive Oxygen Species. Free Radic Biol Med 2011;50:139–147.
    OpenUrlPubMed
  31. 31.↵
    2. Weisburg JH,
    3. Schuck AG,
    4. Reiss SE,
    5. Wolf BJ,
    6. Fertel SR,
    7. Zuckerbraun HL, et al.
    Ellagic Acid, a Dietary Polyphenol, Selectively Cytotoxic to HSC-2 Oral Carcinoma Cells. Anticancer Res 2013;33:1829–1836.
    OpenUrlAbstract/FREE Full Text
  32. 32.↵
    2. Aiyer HS,
    3. Vadhanam MV,
    4. Stoyanova R,
    5. Caprio GD,
    6. Clapper ML,
    7. Gupta RC.
    Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes. Int J Mol Sci 2008;9:327–341.
    OpenUrlCrossRefPubMed
  33. 33.↵
    2. Whitley AC,
    3. Stoner GD,
    4. Darby MV,
    5. Walle T.
    Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid-extensive binding to protein and DNA. Biochem. Pharmacol 2003;66:907–915.
    OpenUrlCrossRefPubMedWeb of Science
  34. 34.↵
    2. Mandal S,
    3. Stoner GD.
    Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid. Carcinogenesis 1990;11:55–61.
    OpenUrlCrossRefPubMedWeb of Science
  35. 35.↵
    2. Siglin JC,
    3. Barch DH,
    4. Stoner GD.
    Effects of dietary phenethyl isothiocyanate, ellagic acid, sulindac and calcium on the induction and progression of N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats. Carcinogenesis 1995;16:1101–1106.
    OpenUrlCrossRefPubMedWeb of Science
  36. 36.↵
    2. Stoner GD,
    3. Chen T,
    4. Kresty LA,
    5. Aziz RM,
    6. Reinemann T,
    7. Nines R.
    Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms. Nutr Cancer 2006;54:33–46.
    OpenUrlCrossRefPubMedWeb of Science
  37. 37.↵
    2. Pitchakarn P,
    3. Chewonarin T,
    4. Ogawa K,
    5. Suzuki S,
    6. Asamoto M,
    7. Takahashi S, et al.
    Ellagic Acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac J Cancer Prev 2013;14:2859–2863.
    OpenUrl
  38. 38.↵
    2. Sartippour MR,
    3. Seeram NP,
    4. Rao JY,
    5. Moro A,
    6. Harris DM,
    7. Henning SM, et al.
    Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo. Int J Oncol 2008;32:475–480.
    OpenUrlPubMedWeb of Science
  39. 39.↵
    2. Huang ST,
    3. Yang RC,
    4. Wu HT,
    5. Wang CN,
    6. Pang JS.
    Zinc-Chelation Contributes to the Anti-Angiogenic Effect of Ellagic Acid on Inhibiting MMP-2 Activity, Cell Migration and Tube Formation. Plos One 2011;6:e18986.
  40. 40.↵
    2. Rocha A,
    3. Wang L,
    4. Penichet M,
    5. Martins-Green M.
    Pomegranate juice and specific components inhibit cell and molecular processes critical for metastasis of breast cancer. Breast Cancer Res Treat 2012;136:647–658.
    OpenUrlCrossRefPubMedWeb of Science
  41. 41.↵
    2. Wang L,
    3. Ho J,
    4. Glackin C,
    5. Martins-Green M.
    Specific pomegranate juice components as potential inhibitors of prostate cancer metastasis. Transl Oncol 2012;5:344–355.
    OpenUrlCrossRefPubMed
  42. 42.↵
    2. Capece D,
    3. Fischietti M,
    4. Verzella D,
    5. Gaggiano A,
    6. Cicciarelli G,
    7. Tessitore A, et al.
    The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed Res Int 2013;2013:187204.
    OpenUrl
  43. 43.↵
    2. Lim KH,
    3. Choi HS,
    4. Park YK,
    5. Park ES,
    6. Shin GC,
    7. Kim DH, et al.
    HBx-induced NF-κB signaling in liver cells is potentially mediated by the ternary complex of HBx with p22-FLIP and NEMO. PLoS One 2013;8:e57331.
  44. 44.
    2. Branda M,
    3. Wands JR.
    Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma. Hepatology 2006;43:891–902.
    OpenUrlCrossRefPubMedWeb of Science
  45. 45.↵
    2. Kremsdorf D,
    3. Soussan P,
    4. Paterlini-Brechot P,
    5. Brechot C.
    Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis. Oncogene 2006;25:3823–3833.
    OpenUrlCrossRefPubMedWeb of Science
  46. 46.↵
    2. Klampfer L.
    Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011;11:451–464.
    OpenUrlCrossRefPubMedWeb of Science
  47. 47.↵
    2. Mowla SN,
    3. Perkins ND,
    4. Jat PS.
    Friend or foe: emerging role of nuclear factor appa-light-chain-enhancer of activated B cells in cell senescence. Onco Targets Ther 2013;6:1221–1229.
    OpenUrl
  48. 48.↵
    2. Arsura M,
    3. Cavin LG.
    Nuclear factor-kappaB and liver carcinogenesis. Cancer Lett 2005;229:157–169.
    OpenUrlCrossRefPubMedWeb of Science
  49. 49.↵
    2. Aggarwal BB,
    3. Shishodia S,
    4. Sandur SK,
    5. Pandey MK,
    6. Sethi G.
    Inflammation and cancer: how hot is the link? Biochem Pharmacol 2006;72:1605–1621.
    OpenUrlCrossRefPubMedWeb of Science
  50. 50.↵
    2. Khan MK,
    3. Ansari IA,
    4. Khan MS.
    Dietary phytochemicals as potent chemotherapeutic agents against breast cancer: Inhibition of NF-κB pathway via molecular interactions in rel homology domain of its precursor protein p105. Pharmacogn Mag 2013;9:51–57.
    OpenUrl
  51. 51.↵
    2. Umesalma S,
    3. Sudhandiran G.
    Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol 2010;107:650–655.
    OpenUrlCrossRefPubMed
  52. 52.↵
    2. Girdhani S,
    3. Bhosle SM,
    4. Thulsidas SA,
    5. Kumar A,
    6. Mishra KP.
    Potential of radiosensitizing agents in cancer chemo-radiotherapy. J Cancer Res Ther 2005;1:129–131.
    OpenUrlPubMed
  53. 53.↵
    2. Nambiar D,
    3. Rajamani P,
    4. Singh RP.
    Effects of phytochemicals on ionization radiation-mediated carcinogenesis and cancer therapy. Mutat Res 2011;728:139–157.
    OpenUrlCrossRefPubMedWeb of Science
  54. 54.↵
    2. Shin MS,
    3. Kang EH,
    4. Lee YI.
    A flavonoid from medicinal plants blocks hepatitis B virus-e antigen secretion in HBV-infected hepatocytes. Antiviral Res 2005;67:163–168.
    OpenUrlCrossRefPubMedWeb of Science
  55. 55.↵
    2. Kang EH,
    3. Kown TY,
    4. Oh GT,
    5. Park WF,
    6. Park SI,
    7. Park SK, et al.
    The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen. Antiviral Res 2006;72:100–106.
    OpenUrlCrossRefPubMedWeb of Science
  56. 56.↵
    2. Yüce A,
    3. Ateşşahin A,
    4. Ceribaşi AO,
    5. Aksakal M.
    Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharmacol Toxicol 2007;101:345–349.
    OpenUrlCrossRefPubMed
  57. 57.↵
    2. Hayeshi R,
    3. Mutingwende I,
    4. Mavengere W,
    5. Masiyanise V,
    6. Mukanganyama S.
    The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin. Food Chem Toxicol 2007;45:286–295.
    OpenUrlCrossRefPubMedWeb of Science
  58. 58.↵
    2. Vicinanza R,
    3. Zhang Y,
    4. Henning SM,
    5. Heber D.
    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 Alternat Med 2013;2013:247504.
    OpenUrlPubMed
  59. 59.↵
    2. González-Sarrías A,
    3. Miguel V,
    4. Merino G,
    5. Lucas R,
    6. Morales JC,
    7. Tomás-Barberán F, et al.
    The gut microbiota ellagic acid-derived metabolite urolithin A and its sulfate conjugate are substrates for the drug efflux transporter breast cancer resistance protein (ABCG2/BCRP). J Agric Food Chem 2013;61:4352–4359.
    OpenUrlCrossRef
  60. 60.↵
    2. González-Sarrías A,
    3. Giménez-Bastida JA,
    4. Núñez-Sánchez MA,
    5. Larrosa M,
    6. García-Conesa MT,
    7. Tomás-Barberán FA, et al.
    Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. Eur J Nutr 2014;53:853–864.
    OpenUrlCrossRefPubMed
  61. 61.↵
    2. Bell C,
    3. Hawthorne S.
    Ellagic acid, pomegranate and prostate cancer -- a mini review. J Pharm Pharmacol 2008;60:139–144.
    OpenUrlCrossRefPubMedWeb of Science
  62. 62.↵
    2. Sharma G,
    3. Italia JL,
    4. Sonaje K,
    5. Tikoo K,
    6. Ravi Kumar MN.
    Biodegradable in situ gelling system for subcutaneous administration of ellagic acid and ellagic acid loaded nanoparticles: evaluation of their antioxidant potential against cyclosporine induced nephrotoxicity in rats. J Control Release 2007;118:27–37.
    OpenUrlCrossRefPubMed
  63. 63.↵
    2. Bala I,
    3. Bhardwaj V,
    4. Hariharan S,
    5. Kharade SV,
    6. Roy N,
    7. Ravi Kumar MN.
    Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration. J Drug Target 2006;14:27–34.
    OpenUrlPubMed
  64. 64.↵
    2. Jeong YI,
    3. Prasad Yv R,
    4. Ohno T,
    5. Yoshikawa Y,
    6. Shibata N,
    7. Kato S, et al.
    Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine. J Pharm Pharmacol 2001;53:1079–1085.
    OpenUrlPubMed
  65. 65.↵
    2. Bansal SS,
    3. Goel M,
    4. Aqil F,
    5. Vadhanam MV,
    6. Gupta RC.
    Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila) 2011;4:1158–1171.
    OpenUrlAbstract/FREE Full Text
  66. 66.↵
    2. Espín JC,
    3. Larrosa M,
    4. García-Conesa MT,
    5. Tomás-Barberán F.
    Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far. Evid Based Complement Alternat Med 2013;2013:270418.
    OpenUrlCrossRefPubMed
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