Multitargeted therapy of cancer by ellagitannins. Cancer Lett

UCLA Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States.
Cancer letters (Impact Factor: 5.62). 06/2008; 269(2):262-8. DOI: 10.1016/j.canlet.2008.03.043
Source: PubMed


Ellagitannins are bioactive polyphenols that have antioxidant and anti-inflammatory bioactivities. Pomegranate juice has the highest concentration of ellagitannins of any commonly consumed juice and contains the unique ellagitannin, punicalagin. Punicalagin is the largest molecular weight polyphenol known. Ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid. They are also metabolized by gut flora into urolithins which are conjugated in the liver and excreted in the urine. These urolithins are also bioactive and inhibit prostate cancer cell growth. Inhibition of Nuclear Factor Kappa-B activation has been shown in prostate cancer cells and in human prostate cancer xenografts in mice. In clinical studies, pomegranate juice administration led to a decrease in the rate of rise of Prostate Specific Antigen after primary treatment with surgery or radiation. Continued translational research on the chemopreventive potential of pomegranate ellagitannins is ongoing.

1 Follower
16 Reads
  • Source
    • "They also inhibit the activity of DNA polymerase α (Saito et al., 2004), P-glycoprotein ( Jodoina et al., 2002), caspases 3, 7 and 2 (Katunuma et al., 2006), and have hypoglycemic properties in vivo (Lu et al., 2011). Ellagitannins and their metabolites formed in the gastrointestinal tract through the action of colonic bacteria (ellagic acid and urolithins A–D) are thought to have chemopreventive properties, especially against colon cancer (Heber, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionPotentilla tormentilla has many biological and pharmacological properties and can be used as an ingredient of some herbal medicines or beverages.Objective The aim of this study was to evaluate the content of individual polyphenols, especially condensed and hydrolysable tannins in commercially available tormentil rhizomes and tinctures using chromatographic methods.MethodsA quantitative analysis (HPLC-PDA) was preceded by qualitative studies (UPLC-qTOF-MS/MS) and the isolation (CC) of the major tannin compounds.ResultsThe tested plant material is characterised by a high content of tannins and related polyphenols, i.e. in rhizomes even at the level above 20% and in tinctures above 2%. The main components of tormentil rhizomes are procyanidin B3 (mean ~ 3.6%), procyanidin C2 (mean ~ 2.8%), agrimoniin (mean ~ 2.5%), 3-O-galloylquinic acid (mean ~ 1.7%), catechin (mean ~ 1.6%), other flavan-3-ol oligomers (mean ~ 0.5–1.1) and laevigatins (mean ~ 0.2–0.6%). Free ellagic acid and glycosides of ellagic and methylellagic acids are secondary components.Conclusions Underground parts of tormentil are a source of oligomeric proanthocyanidins and ellagitannins, but in smaller quantity of gallotannins. Monogalloylquinic acids are new identified compounds, which had not been described in Potentilla tormentilla before we started our research. In the analysed tormentil tinctures agrimoniin concentration is lower in relation to other tannins. Copyright © 2015 John Wiley & Sons, Ltd.
    Phytochemical Analysis 06/2015; 26(5). DOI:10.1002/pca.2570 · 2.34 Impact Factor
  • Source
    • "), to induce cell cycle arrest and apoptosis, and to act as cancer chemopreventive agents in a multitude of preclinical and animal studies (Hagiwara et al. 2010; Heber 2008; Ngo et al. 2011; Petersen and Simmonds 2003; Singh et al. 2011; Viladomiu et al. 2013; Wu and Wang 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigallocatechin gallate (EGCG), ellagic acid (EA) and rosmarinic acid (RA) are natural polyphenols exerting cancer chemopreventive effects. Ribonucleotide reductase (RR; EC converts ribonucleoside diphosphates into deoxyribonucleoside diphosphates being essential for DNA replication, which is why the enzyme is considered an excellent target for anticancer therapy. EGCG, EA, and RA dose-dependently inhibited the growth of human HL-60 promyelocytic leukemia cells, exerted strong free radical scavenging potential, and significantly imbalanced nuclear deoxyribonucleoside triphosphate (dNTP) concentrations without distinctly affecting the protein levels of RR subunits (R1, R2, p53R2). Incorporation of (14)C-cytidine into nascent DNA of tumor cells was also significantly lowered, being equivalent to an inhibition of DNA synthesis. Consequently, treatment with EGCG and RA attenuated cells in the G0/G1 phase of the cell cycle, finally resulting in a pronounced induction of apoptosis. Sequential combination of EA and RA with the first-line antileukemic agent arabinofuranosylcytosine (AraC) synergistically potentiated the antiproliferative effect of AraC, whereas EGCG plus AraC yielded additive effects. Taken together, we show for the first time that EGCG, EA, and RA perturbed dNTP levels and inhibited cell proliferation in human HL-60 promyelocytic leukemia cells, with EGCG and RA causing a pronounced induction of apoptosis. Due to these effects and synergism with AraC, these food ingredients deserve further preclinical and in vivo testing as inhibitors of leukemic cell proliferation. Copyright © 2014 Elsevier GmbH. All rights reserved.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 01/2015; 22(1):213-22. DOI:10.1016/j.phymed.2014.11.017 · 3.13 Impact Factor
  • Source
    • "The total EA quantities of different fruits and plants are provided in Table 1. EA exerts potent preventive and therapeutic effects against several types of cancers, including colon cancer, breast cancer, prostate cancer, skin cancer, esophageal cancer, and osteogenic sarcoma14,15. The anticarcinogenic properties of EA have drawn increasing attention globally. "
    [Show abstract] [Hide abstract]
    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.
    Cancer Biology and Medicine 06/2014; 11(2):92-100. DOI:10.7497/j.issn.2095-3941.2014.02.004
Show more

Similar Publications