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Lookup NU author(s): Dr Tetsushi Kataura, Dr Viktor Korolchuk
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs.
Author(s): Neves SP, Bomfim LM, Kataura T, Carvalho SG, Nogueira ML, Dias RB, Valverde LDF, Gurgel Rocha CA, Soares MBP, Silva MMD, Batista AA, Korolchuk VI, Bezerra DP
Publication type: Article
Publication status: Published
Journal: Biomedicine and Pharmacotherapy
Year: 2024
Volume: 177
Print publication date: 01/08/2024
Online publication date: 01/07/2024
Acceptance date: 02/04/2024
Date deposited: 15/07/2024
ISSN (print): 0753-3322
ISSN (electronic): 1950-6007
Publisher: Elsevier Masson s.r.l.
URL: https://doi.org/10.1016/j.biopha.2024.117059
DOI: 10.1016/j.biopha.2024.117059
PubMed id: 38955086
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