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RETRACTED: Disulfiram Chelated With Copper Inhibits the Growth of Gastric Cancer Cells by Modulating Stress Response and Wnt/β-catenin Signaling.

Authors :
Ling Wang
Xiaoke Chai
Run Wan
Hong Zhang
Cong Zhou
Lin Xiang
Paul, Maswikiti Ewetse
Yumin Li
Source :
Frontiers in Oncology; 2024, p1-19, 19p
Publication Year :
2024

Abstract

Disulfiram (DSF) is a well-known drug for alcohol abuse. In recent decades, DSF has been demonstrated to exhibit anti-tumor activity; DSF chelated with copper shows enhanced anti-tumor effect. Our goal was to explore the effect of DSF/Cu complex on the growth and metastasis of gastric cancer (GC) in vitro and in vivo. DSF/Cu complex suppressed the proliferation, migration of MKN-45 and BGC-823 GC cells. Furthermore, DSF/Cu treatment reduced the tumor volume in GC mouse models with a tumor suppression rate of 48.24%. Additionally, DSF/Cu induced apoptosis in vitro in MKN-45 and BGC-823 GC cells in a dose- and time-dependent manner as well as in vivo in the xenograft tumor mouse model. Furthermore, DSF/Cu induced autophagy and autophagic flux in MKN-45 and BGC-823 cells, increased the expression of autophagy-related Beclin-1 and LC3 proteins in vivo. Additionally, DSF/Cu suppressed aerobic glycolysis and oxidative phosphorylation by reducing oxygen consumption rate and extracellular acidification rate, respectively, in MKN-45 and BGC-823 cells. Treatment with DSF/Cu induced oxidative stress and DNA damage response by elevating the reactive oxygen species levels; increasing the expression of P53, P21, and g-H2AX proteins; and inhibiting Wnt/bcatenin signaling in vitro and in vivo. Thus, DSF/Cu suppressed the growth and metastasis of GC cells via modulating the stress response and Wnt/b-catenin signaling. Hence, DSF may be used as a potential therapeutic agent for the treatment of GC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
2234943X
Database :
Complementary Index
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
179593931
Full Text :
https://doi.org/10.3389/fonc.2020.595718