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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 |
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 |
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1-s2.0-S0223523419306452.pdf | Makale (Article) | 3.14 MB | Adobe PDF | ![]() View/Open |
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