Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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  • Article
    Citation - WoS: 15
    Citation - Scopus: 15
    Sorafenib Loaded Zif-8 Metal-Organic Frameworks as a Multifunctional Nano-Carrier Offers Effective Hepatocellular Carcinoma Therapy
    (Elsevier, 2023) Mete, Derya; Yemeztaşlıca Yetişkin, Egehan; Şanlı Mohamed, Gülşah
    Hepatocellular carcinoma (HCC) is a primary malignant neoplasia of the liver and sorafenib is one of the most commonly used drugs in the treatment of HCC. Due to undesirable nature and side effects of sorafenib, nano-drug delivery systems are being developed. A member of metal-organic frameworks (MOFs), ZIF-8 offers a very suitable platform for drug transport and controlled drug release due to its zinc content and pH-sensitive, biodegradable in an acidic environment. In the present study, sorafenib was encapsulated in ZIF-8 material with 53.8% efficiency and 58% loading capacity (SRF@ZIF-8). Structural characterizations of synthesized ZIF-8 and SRF@ZIF-8 system were investigated in details. Drug release analysis exhibited a faster release profile at pH 5.0 compared to that of pH 7.4. The cytotoxic effects of sorafenib and zinc were investigated in HepG2 and HuH-7 cell lines in vitro. The results demonstrated that in addition to sorafenib, ZIF-8 provided zinc to the envi-ronment with its biodegradable structure resulted in an effective cytotoxic effect on HCC cells. The findings showed that a formulation combining zinc and sorafenib together was more effective in HCC treatment compared to sorafenib itself.
  • Article
    Citation - WoS: 16
    Citation - Scopus: 17
    Antiproliferative Activity of (r)-4 '-methylklavuzon on Hepatocellular Carcinoma Cells and Epcam(+)/Cd133(+) Cancer Stem Cells Via Sirt1 and Exportin-1 (crm1) Inhibition
    (Elsevier Ltd., 2019) Delman, Murat; Avcı, Sanem Tercan; Akçok, İsmail; Kanbur, Tuğçe; Erdal, Esra; Çağır, Ali
    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.