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      Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin

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          Abstract

          Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus) Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) and B-cell lymphoma 2 (Bcl-2), and inducing Bcl-2-associated agonist of cell death (BAD) phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances.

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          Most cited references37

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          Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells.

          Chromatin is a dynamic macromolecular structure epigenetically modified to regulate specific gene expression. Altered chromatin function can lead to aberrant expression of growth regulators and may, ultimately, cause cancer. That many human diseases have epigenetic etiology has stimulated the development of 'epigenetic' therapies. Inhibitors of histone deacetylases (HDACIs) induce proliferation arrest, maturation and apoptosis of cancer cells, but not normal cells, in vitro and in vivo, and are currently being tested in clinical trials. We investigated the mechanism(s) underlying this tumor selectivity. We report that HDACIs induce, in addition to p21, expression of TRAIL (Apo2L, TNFSF10) by directly activating the TNFSF10 promoter, thereby triggering tumor-selective death signaling in acute myeloid leukemia (AML) cells and the blasts of individuals with AML. RNA interference revealed that the induction of p21, TRAIL and differentiation are separable activities of HDACIs. HDACIs induced proliferation arrest, TRAIL-mediated apoptosis and suppression of AML blast clonogenicity irrespective of French-American-British (FAB) classification status, karyotype and immunophenotype. No apoptosis was seen in normal CD34(+) progenitor cells. Our results identify TRAIL as a mediator of the anticancer action of HDACIs.
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            Lichens—a promising source of bioactive secondary metabolites

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              Pharmaceutically relevant metabolites from lichens.

              K. Müller (2001)
              Lichen metabolites exert a wide variety of biological actions including antibiotic, antimycobacterial, antiviral, antiinflammatory, analgesic, antipyretic, antiproliferative and cytotoxic effects. Even though these manifold activities of lichen metabolites have now been recognized, their therapeutic potential has not yet been fully explored and thus remains pharmaceutically unexploited. In this mini-review, particular attention is paid to the most common classes of small-molecule constituents of lichens, from both the chemical viewpoint and with regard to possible therapeutic implications. In particular, aliphatic acids, pulvinic acid derivatives, depsides and depsidones, dibenzofuans, anthraquinones, naphthoquinones as well as epidithiopiperazinediones are described. An improved access to these lichen substances in drug discovery high-throughput screening programs will provide impetus for identifying novel lead-compounds with therapeutic potential and poses new challenges for medicinal chemistry.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 April 2015
                April 2015
                : 16
                : 4
                : 7861-7875
                Affiliations
                [1 ]Department of Biological Sciences—Plant Biology Section, University of Naples “Federico II”, Naples 80126, Italy; E-Mails: adbasile@ 123456unina.it (A.B.); bbconte@ 123456yahoo.it (B.C.); francesca.deruberto@ 123456gmail.com (F.D.R.)
                [2 ]Department of Pharmacy, University of Naples “Federico II”, Naples 80131, Italy; E-Mail: drigano@ 123456unina.it
                [3 ]Department of Life Sciences, University of Siena, Siena 53100, Italy; E-Mails: stefano.loppi@ 123456unisi.it (S.L.); paoli4@ 123456unisi.it (L.P.)
                [4 ]Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples 80138, Italy; E-Mails: annalisa.disanti@ 123456unina.it (A.D.S.); angela.nebbioso@ 123456unina2.it (A.N.); annamaria.molinari@ 123456unina2.it (A.M.M.)
                [5 ]Interdepartmental Service Centre for Electron Microscopy C.I.S.M.E., University of Naples “Federico II”, via Foria 223, Naples 80139, Italy; E-Mail: sergio.sorbo@ 123456unina.it
                [6 ]Institute of Genetics and Biophysics (IGB), Adriano Buzzati Traverso, Naples 80131, Italy
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mails: lucia.altucci@ 123456unina2.it (L.A.); paola.bontempo@ 123456unina2.it (P.B.); Tel.: +39-081-566-7569 (L.A.); +39-081-566-5702 (P.B.); Fax: +39-081-450-169 (L.A. & P.B.).
                Article
                ijms-16-07861
                10.3390/ijms16047861
                4425054
                25860944
                b07f9365-6e87-4fc8-9f9e-2e1887324522
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 January 2015
                : 31 March 2015
                Categories
                Article

                Molecular biology
                xanthoria parietina,lichens,parietin,antimicrobial activity,anticancer activity,signal transduction,proliferation,differentiation

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