Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/8927
Title: Antiproliferative activity of (R)-4 '-methylklavuzon on hepatocellular carcinoma cells and EpCAM(+)/CD133(+) cancer stem cells via SIRT1 and Exportin-1 (CRM1) inhibition
Authors: Delman, Murat
Avcı, Sanem Tercan
Akçok, İsmail
Kanbur, Tuğçe
Erdal, Esra
Çağır, Ali
Keywords: Hepatocellular carcinoma
Cancer stem cell
SIRT1 inhibitor
CRM1 inhibitor
Topoisomerase I inhibitor
Klavuzon
Issue Date: Oct-2019
Publisher: Elsevier Ltd.
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: PubMed: 31306909
URI: https://doi.org/10.1016/j.ejmech.2019.07.024
https://hdl.handle.net/11147/8927
ISSN: 0223-5234
1768-3254
0223-5234
1768-3254
Appears in Collections:Bioengineering / Biyomühendislik
Chemistry / Kimya
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Files in This Item:
File Description SizeFormat 
1-s2.0-S0223523419306452.pdf
  Until 2023-01-01
Makale (Article)3.14 MBAdobe PDFView/Open    Request a copy
Show full item record

CORE Recommender

SCOPUSTM   
Citations

4
checked on Nov 27, 2021

WEB OF SCIENCETM
Citations

6
checked on Nov 27, 2021

Page view(s)

30
checked on Nov 27, 2021

Google ScholarTM

Check

Altmetric


Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.