Research progress on the anticarcinogenic actions and mechanisms of ellagic acid

Hong-Mei Zhang, Lei Zhao, Hao Li, Hao Xu, Wen-Wen Chen, Lin Tao, Hong-Mei Zhang, Lei Zhao, Hao Li, Hao Xu, Wen-Wen Chen, Lin Tao

Abstract

Cancer is a leading cause of death worldwide. Cancer treatments by chemotherapeutic agents, surgery, and radiation have not been highly effective in reducing the incidence of cancers and increasing the survival rate of cancer patients. In recent years, plant-derived compounds have attracted considerable attention as alternative cancer remedies for enhancing cancer prevention and treatment because of their low toxicities, low costs, and low side effects. Ellagic acid (EA) is a natural phenolic constituent. Recent in vitro and in vivo experiments have revealed that EA elicits anticarcinogenic effects by inhibiting tumor cell proliferation, inducing apoptosis, breaking DNA binding to carcinogens, blocking virus infection, and disturbing inflammation, angiogenesis, and drug-resistance processes required for tumor growth and metastasis. This review enumerates the anticarcinogenic actions and mechanisms of EA. It also discusses future directions on the applications of EA.

Keywords: Ellagic acid (EA); cancer; mechanism.

Conflict of interest statement

No potential conflicts of interest are disclosed.

References

    1. Boyle P, Levin B. eds. World Cancer Report 2008. International Agency for Research on Cancer, 1-260.
    1. Ramasamy S, Abdul Wahab N, Zainal Abidin N, Manickam S, Zakaria Z.Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction. PLoS One 2012;7:e34793.
    1. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005;100:72-79
    1. Girish C, Pradhan SC. Drug development for liver diseases: focus on picroliv, ellagic acid and curcumin. Fundam Clin Pharmacol 2008;22:623-632
    1. Williner MR, Pirovani ME, Güemes DR. Ellagic acid content in strawberries of different cultivars and ripening stages. J Sci Food Agric 2003;83:842-845
    1. Bakkalbaşi E, Menteş O, Artik N.Food ellagitannins-occurrence, effects of processing and storage. Crit Rev Food Sci Nutr 2009;49:283-298
    1. Daniel EM, Krupnick AS, Heur YH, Blinzler JA, Nims RW, Stoner GD. Extraction, stability and, quantitation of ellagic acid in various fruits and nuts. J Food Compost Anal 1989;2:338-349
    1. Häkkinen S, Heinonen M, Kärenlampi S, Mykkänen H, Ruuskanen J, Törrönen R.Screening of selected flavanoids and phenolic acids in 19 berries. Food Research International 1999;32:345-353
    1. Atkinson CJ, Dodds PA, Ford YY, Le Mière J, Taylor JM, 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
    1. Sajid ZI, Anwar F, Shabir G, Rasul G, Alkharfy KM, 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
    1. Wu QY, Zhou Y, Jin X, Guan Y, Xu M, 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
    1. Lee JH, Johnson JV, 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
    1. Heber D.Multitargeted therapy of cancer by ellagitannins. Cancer Letters 2008;269:262-268
    1. Wang N, Wang ZY, Mo SL, Loo TY, Wang DM, 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
    1. Vanella L, Di Giacomo C, Acquaviva R, Barbagallo I, Cardile V, Kim DH, et al. Apoptotic markers in a prostate cancer cell line: Effect of ellagic acid. Oncol Rep 2013;30:2804-2810
    1. Han DH, Lee MJ, Kim JH. Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer research 2006;26:3601-3606
    1. Edderkaoui M, Odinokova I, Ohno I, Gukovsky I, Go VL, 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
    1. Edderkaoui M, Lugea A, Hui H, Eibl G, Lu QY, 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
    1. Zhao M, Tang SN, Marsh JL, Shankar S, Srivastava RK. Ellagic acid inhibits human pancreatic cancer growth in Balb/C nude mice. Cancer Lett 2013;337:210-217
    1. Chung YC, Lu LC, Tsai MH, Chen YJ, Chen YY, 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.
    1. Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH. Phyllanthus urinaria Increases Apoptosis and Reduces Telomerase Activity in Human Nasopharyngeal Carcinoma Cells. Forsch Komplementmed 2009;16:34-40
    1. Mishra S, Vinayak M.Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway. Mol Biol Rep 2013;40:1417-1428
    1. Mishra S, 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
    1. Aiyer HS, Warri AM, Wood DR E, Hilakivi-Clarke L, 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
    1. Aiyer HS, 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
    1. Aqil F, Gupta A, Munagala R, Jeyabalan J, Kausar H, Sharma RJ, et al. Antioxidant and antiproliferative activities of anthocyanin/ellagitannin-enriched extracts from Syzygium cumini L. Nutr Cancer 2012;64:428-438
    1. Priyadarsini KI, Khopde SM, Kumar SS, Mohan H. Free radical studies of ellagic acid, a natural phenolic antioxidant. J Agric Food Chem 2002;50:2200-2206
    1. Gerhäuser C, Klimo K, Heiss E, Neumann I, Gamal-Eldeen A, Knauft J, et al. Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat Res 2003;523-524:163-172
    1. Spencer WA, Jeyabalan J, Kichambre S, 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
    1. Weisburg JH, Schuck AG, Reiss SE, Wolf BJ, Fertel SR, Zuckerbraun HL, et al. Ellagic Acid, a Dietary Polyphenol, Selectively Cytotoxic to HSC-2 Oral Carcinoma Cells. Anticancer Res 2013;33:1829-1836
    1. Aiyer HS, Vadhanam MV, Stoyanova R, Caprio GD, Clapper ML, 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
    1. Whitley AC, Stoner GD, Darby MV, 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
    1. Mandal S, Stoner GD. Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid. Carcinogenesis 1990;11:55-61
    1. Siglin JC, Barch DH, 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
    1. Stoner GD, Chen T, Kresty LA, Aziz RM, Reinemann T, Nines R. Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms. Nutr Cancer 2006;54:33-46
    1. Pitchakarn P, Chewonarin T, Ogawa K, Suzuki S, Asamoto M, Takahashi S, et al. Ellagic Acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac J Cancer Prev 2013;14:2859-2863
    1. Sartippour MR, Seeram NP, Rao JY, Moro A, Harris DM, 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
    1. Huang ST, Yang RC, Wu HT, Wang CN, 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.
    1. Rocha A, Wang L, Penichet M, 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
    1. Wang L, Ho J, Glackin C, Martins-Green M.Specific pomegranate juice components as potential inhibitors of prostate cancer metastasis. Transl Oncol 2012;5:344-355
    1. Capece D, Fischietti M, Verzella D, Gaggiano A, Cicciarelli G, Tessitore A, et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed Res Int 2013;2013:187204.
    1. Lim KH, Choi HS, Park YK, Park ES, Shin GC, 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.
    1. Branda M, Wands JR. Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma. Hepatology 2006;43:891-902
    1. Kremsdorf D, Soussan P, Paterlini-Brechot P, Brechot C.Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis. Oncogene 2006;25:3823-3833
    1. Klampfer L.Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011;11:451-464
    1. Mowla SN, Perkins ND, 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
    1. Arsura M, Cavin LG. Nuclear factor-kappaB and liver carcinogenesis. Cancer Lett 2005;229:157-169
    1. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol 2006;72:1605-1621
    1. Khan MK, Ansari IA, 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
    1. Umesalma S, 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
    1. Girdhani S, Bhosle SM, Thulsidas SA, Kumar A, Mishra KP. Potential of radiosensitizing agents in cancer chemo-radiotherapy. J Cancer Res Ther 2005;1:129-131
    1. Nambiar D, Rajamani P, Singh RP. Effects of phytochemicals on ionization radiation-mediated carcinogenesis and cancer therapy. Mutat Res 2011;728:139-157
    1. Shin MS, Kang EH, Lee YI. A flavonoid from medicinal plants blocks hepatitis B virus-e antigen secretion in HBV-infected hepatocytes. Antiviral Res 2005;67:163-168
    1. Kang EH, Kown TY, Oh GT, Park WF, Park SI, 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
    1. Yüce A, Ateşşahin A, Ceribaşi AO, Aksakal M. Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharmacol Toxicol 2007;101:345-349
    1. Hayeshi R, Mutingwende I, Mavengere W, Masiyanise V, 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
    1. Vicinanza R, Zhang Y, Henning SM, 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.
    1. González-Sarrías A, Miguel V, Merino G, Lucas R, Morales JC, 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
    1. González-Sarrías A, Giménez-Bastida JA, Núñez-Sánchez MA, Larrosa M, García-Conesa MT, 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
    1. Bell C, Hawthorne S.Ellagic acid, pomegranate and prostate cancer -- a mini review. J Pharm Pharmacol 2008;60:139-144
    1. Sharma G, Italia JL, Sonaje K, Tikoo K, 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
    1. Bala I, Bhardwaj V, Hariharan S, Kharade SV, Roy N, 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
    1. Jeong YI, Prasad Yv R, Ohno T, Yoshikawa Y, Shibata N, 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
    1. Bansal SS, Goel M, Aqil F, Vadhanam MV, Gupta RC. Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila) 2011;4:1158-1171
    1. Espín JC, Larrosa M, García-Conesa MT, 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.

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