Article

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

ABSTRACT 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.

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    • "), 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). "
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    ABSTRACT: Epigallocatechin gallate (EGCG), ellagic acid (EA) and rosmarinic acid (RA) are natural polyphenols exerting cancer chemopreventive effects. Ribonucleotide reductase (RR; EC 1.17.4.1) 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 · 2.88 Impact Factor
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    • "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. "
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    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.
    06/2014; 11(2):92-100. DOI:10.7497/j.issn.2095-3941.2014.02.004
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    • "PC and EA have antioxidant functions and possess strong anti-inflammatory, antiproliferative, hepatoprotective, and antigenotoxic properties [20] [21] [22] [23]. PC and EA also exhibit anticancer properties in vitro and in vivo [17] [24]. However, studies on antimutagenic potential on these compounds are scanty. "
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    ABSTRACT: Punicalagin (PC) is an ellagitannin found in the fruit peel of Punica granatum. We have demonstrated antioxidant and antigenotoxic properties of Punica granatum and showed that PC and ellagic acid (EA) are its major constituents. In this study, we demonstrate the antimutagenic potential, inhibition of BP-induced DNA damage, and antiproliferative activity of PC and EA. Incubation of BP with rat liver microsomes, appropriate cofactors, and DNA in the presence of vehicle or PC and EA showed significant inhibition of the resultant DNA adducts, with essentially complete inhibition (97%) at 40 μ M by PC and 77% inhibition by EA. Antimutagenicity was tested by Ames test. PC and EA dose-dependently and markedly antagonized the effect of tested mutagens, sodium azide, methyl methanesulfonate, benzo[a]pyrene, and 2-aminoflourine, with maximum inhibition of mutagenicity up to 90 percent. Almost all the doses tested (50-500 μ M) exhibited significant antimutagenicity. A profound antiproliferative effect on human lung cancer cells was also shown with PC and EA. Together, our data show that PC and EA are pomegranate bioactives responsible for inhibition of BP-induced DNA adducts and strong antimutagenic, antiproliferative activities. However, these compounds are to be evaluated in suitable animal model to assess their therapeutic efficacy against cancer.
    BioMed Research International 05/2014; 2014:467465. DOI:10.1155/2014/467465 · 2.71 Impact Factor
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