1 Ocak 2019 Dergi makalesi Açık Erişim

Delman, Murat; Avci, Sanem Tercan; Akcok, Ismail; Kanbur, Tugce; Erdal, Esra; Cagir, Ali

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/74491</identifier>
  <creators>
    <creator>
      <creatorName>Delman, Murat</creatorName>
      <givenName>Murat</givenName>
      <familyName>Delman</familyName>
      <affiliation>Izmir Inst Technol, Dept Biotechnol &amp; Bioengn, TR-35430 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Avci, Sanem Tercan</creatorName>
      <givenName>Sanem Tercan</givenName>
      <familyName>Avci</familyName>
    </creator>
    <creator>
      <creatorName>Akcok, Ismail</creatorName>
      <givenName>Ismail</givenName>
      <familyName>Akcok</familyName>
      <affiliation>Izmir Inst Technol, Fac Sci, Dept Chem, TR-35430 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Kanbur, Tugce</creatorName>
      <givenName>Tugce</givenName>
      <familyName>Kanbur</familyName>
      <affiliation>Izmir Inst Technol, Fac Sci, Dept Chem, TR-35430 Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Erdal, Esra</creatorName>
      <givenName>Esra</givenName>
      <familyName>Erdal</familyName>
    </creator>
    <creator>
      <creatorName>Cagir, Ali</creatorName>
      <givenName>Ali</givenName>
      <familyName>Cagir</familyName>
      <affiliation>Izmir Inst Technol, Fac Sci, Dept Chem, TR-35430 Izmir, Turkey</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Antiproliferative Activity Of (R)-4 '-Methylklavuzon On Hepatocellular Carcinoma Cells And Epcam(+)/Cd133(+) Cancer Stem Cells Via Sirt1 And Exportin-1 (Crm1) Inhibition</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2019</publicationYear>
  <dates>
    <date dateType="Issued">2019-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/74491</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.ejmech.2019.07.024</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Cytotoxic effects of (R)-4'-methylklavuzon were investigated on hepatocellular carcinoma cells (HuH-7 and HepG2) and HuH-7 EpCAM(+)/CD133(+) cancer stem cells. IC50 of (R)-4'-methylklavuzon was found as 1.25 mu M for HuH-7 parental cells while it was found as 2.50 mu M for HuH-7 EpCAM(+)/CD133(+) cancer stem cells. (R)-4'-methylklavuzon tended to show more efficient in vitro cytotoxicity with its lower IC50 values on hepatocellular carcinoma cell lines compared to its lead molecule, goniothalamin and FDA-approved drugs, sorafenib and regorafenib. Cell-based Sirtuin/HDAC enzyme activity measurements revealed that endogenous Sirtuin/HDAC enzymes were reduced by 40% compared to control. SIRT1 protein levels were upregulated indicating triggered DNA repair mechanism. p53 was overexpressed in HepG2 cells. (R)-4'methylklavuzon inhibited CRM1 protein providing increased retention of p53 and RIOK2 protein in the nucleus. HuH-7 parental and EpCAM(+)/CD133(+) cancer stem cell spheroids lost intact morphology. 3D HepG2 spheroid viabilities were decreased in a correlation with upregulation in p53 protein levels. (C) 2019 Elsevier Masson SAS. All rights reserved.</description>
  </descriptions>
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