1 Ocak 2019 Dergi makalesi Açık Erişim

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

Citation Style Language JSON

{
  "DOI": "10.1016/j.ejmech.2019.07.024", 
  "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.", 
  "author": [
    {
      "family": "Delman", 
      "given": " Murat"
    }, 
    {
      "family": "Avci", 
      "given": " Sanem Tercan"
    }, 
    {
      "family": "Akcok", 
      "given": " Ismail"
    }, 
    {
      "family": "Kanbur", 
      "given": " Tugce"
    }, 
    {
      "family": "Erdal", 
      "given": " Esra"
    }, 
    {
      "family": "Cagir", 
      "given": " Ali"
    }
  ], 
  "container_title": "EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY", 
  "id": "74491", 
  "issued": {
    "date-parts": [
      [
        2019, 
        1, 
        1
      ]
    ]
  }, 
  "page": "224-237", 
  "title": "Antiproliferative activity of (R)-4 '-methylklavuzon on hepatocellular carcinoma cells and EpCAM(+)/CD133(+) cancer stem cells via SIRT1 and Exportin-1 (CRM1) inhibition", 
  "type": "article-journal", 
  "volume": "180"
}