1 Ocak 2019 Dergi makalesi Açık Erişim

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

Dublin Core

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  <dc:creator>Delman, Murat</dc:creator>
  <dc:creator>Avci, Sanem Tercan</dc:creator>
  <dc:creator>Akcok, Ismail</dc:creator>
  <dc:creator>Kanbur, Tugce</dc:creator>
  <dc:creator>Erdal, Esra</dc:creator>
  <dc:creator>Cagir, Ali</dc:creator>
  <dc:date>2019-01-01</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/74491</dc:identifier>
  <dc:identifier>oai:zenodo.org:74491</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 180 224-237</dc:source>
  <dc:title>Antiproliferative activity of (R)-4 '-methylklavuzon on hepatocellular carcinoma cells and EpCAM(+)/CD133(+) cancer stem cells via SIRT1 and Exportin-1 (CRM1) inhibition</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
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