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      Antiproliferative Effect of Indole Phytoalexins

      review-article
      1 , 2 , 3 , 1 , *
      Molecules
      MDPI
      indole phytoalexins, crucifers, brassinin, antiproliferative, cancer

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          Abstract

          Indole phytoalexins from crucifers have been shown to exhibit significant anti-cancer, chemopreventive, and antiproliferative activity. Phytoalexins are natural low molecular antimicrobial compounds that are synthesized and accumulated in plants after their exposure to pathogenic microorganisms. Most interestingly, crucifers appear to be the only plant family producing sulfur-containing indole phytoalexins. The mechanisms underlying its anti-cancer properties are unknown. Isolation from cruciferous plants does not provide sufficient quantities of indole phytoalexins and, for biological screening, they are usually obtainable through synthesis. Understanding the molecular mechanism of the action of these substances and their structure-activity relationships is quite important in the development of new analogs with a more favorable profile of biological activities. In this review, we present the key features of indole phytoalexins, mainly their antiproliferative ativities.

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          Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention.

          The signal transducers and activators of transcription (STAT)factors function as downstream effectors of cytokine and growth factor receptor signaling. Compared with normal cells and tissues, constitutively activated STATs have been detected in a wide variety of human cancer cell lines and primary tumors. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulated process. In tumor cells, constitutive activation of STATs is linked to persistent activity of tyrosine kinases, including Src, epidermal growth factor receptor, Janus kinases, Bcr-Abl, and many others. Such oncogenic tyrosine kinases are often activated as a consequence of permanent ligand/receptor engagement in autocrine or paracrine cytokine and growth factor signaling or represent autonomous constitutively active enzymes as a result of genetic alterations found in tumor but not normal cells. Persistent signaling of specific STATs, in particular Stat3 and Stat5, has been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis. STATs participate in oncogenesis through up-regulation of genes encoding apoptosis inhibitors and cell cycle regulators such as Bcl-x(L), Mcl-1, cyclins D1/D2, and c-Myc. Inhibition of constitutively active STAT signaling pathways has been shown repeatedly to inhibit tumor cell growth in vitro and in vivo and provides a novel means for therapeutic intervention in human cancer. In this review, we will: (a) explain the mechanisms of STAT activation in normal and malignant signaling; (b) summarize recent evidence for the critical role of constitutively activated Stat3 and Stat5 in oncogenesis; (c) identify candidate STAT target genes implicated in tumor progression; and (d) discuss molecular and pharmacological strategies to interfere with STAT signaling for potential therapeutic intervention in human cancer.
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            Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity.

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              Induced systemic resistance (ISR) against pathogens in the context of induced plant defences.

              M Heil (2002)
              Induced systemic resistance (ISR) of plants against pathogens is a widespread phenomenon that has been intensively investigated with respect to the underlying signalling pathways as well as to its potential use in plant protection. Elicited by a local infection, plants respond with a salicylic-dependent signalling cascade that leads to the systemic expression of a broad spectrum and long-lasting disease resistance that is efficient against fungi, bacteria and viruses. Changes in cell wall composition, de novo production of pathogenesis-related-proteins such as chitinases and glucanases, and synthesis of phytoalexins are associated with resistance, although further defensive compounds are likely to exist but remain to be identified. In this Botanical Briefing we focus on interactions between ISR and induced resistance against herbivores that is mediated by jasmonic acid as a central signalling molecule. While many studies report cross-resistance, others have found trade-offs, i.e. inhibition of one resistance pathway by the other. Here we propose a framework that explains many of the thus far contradictory results. We regard elicitation separately from signalling and from production, i.e. the synthesis of defensive compounds. Interactions on all three levels can act independently from each other.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                26 November 2016
                December 2016
                : 21
                : 12
                : 1626
                Affiliations
                [1 ]Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, 040 11 Košice, Slovakia; chripkova.martina@ 123456gmail.com
                [2 ]Department of Human and Clinical Pharmacology, University of Veterinary Medicine and Pharmacy, 040 11 Košice, Slovakia
                [3 ]Department of Animal Breeding, University of Veterinary Medicine and Pharmacy, 040 11 Košice, Slovakia; frantisek.zigo@ 123456uvlf.sk
                Author notes
                [* ]Correspondence: jan.mojzis@ 123456upjs.sk ; Tel.: +421-552-303-485
                Article
                molecules-21-01626
                10.3390/molecules21121626
                6274154
                27898039
                02f232c6-0ced-4e6e-a6c7-2f32833a0abb
                © 2016 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 (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 October 2016
                : 22 November 2016
                Categories
                Review

                indole phytoalexins,crucifers,brassinin,antiproliferative,cancer

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