The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways

Zhang, Jun; Pu, Ke; Bai, Su-Ping; Peng, Yu-Kui; Fan, Li; Ji, Rui; Guo, Qinghong; Sun, Weiming; Wang, Yuping

doi:10.1177/0300060520925996

Cited by 15 publications

(7 citation statements)

References 24 publications

(26 reference statements)

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“…DSF/Cu complex has been reported to suppress the growth and metastasis of non-small-cell lung cancer (NSCLC), hepatocellular carcinoma, and oral squamous cell carcinoma (6,19,20). Zhang et al found that disulfiram repressed the viability and progression of gastric cancer cells, and inhibited the expression of Wnt/b-catenin by ELISA (21). Therefore, we aimed at exploring the anti-cancer activity of DSF/ Cu complex using MKN-45 and BGC-823 GC cells.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2020

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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 γ-H2AX proteins; and inhibiting Wnt/β-catenin signaling in vitro and in vivo. Thus, DSF/Cu suppressed the growth and metastasis of GC cells via modulating the stress response and Wnt/β-catenin signaling. Hence, DSF may be used as a potential therapeutic agent for the treatment of GC.

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Section: Discussionmentioning

confidence: 99%

“…Zhang et al. found that disulfiram repressed the viability and progression of gastric cancer cells, and inhibited the expression of Wnt/β-catenin by ELISA ( 21 ). Therefore, we aimed at exploring the anti-cancer activity of DSF/Cu complex using MKN-45 and BGC-823 GC cells.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Despite showing promising results in experimental models, bortezomib has not been used for therapy of human GC. Interestingly, disulfiram, a well-known drug for treatment of chronic alcoholism, can inhibit the 26S proteasome and NF-κB activity and demonstrate anti-tumor activities [ 163 ].…”

Section: Therapeutic Targeting Of Nf-κb In Gastric Cancermentioning

confidence: 99%

NF-κB in Gastric Cancer Development and Therapy

et al. 2021

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Gastric cancer is considered one of the most common causes of cancer-related death worldwide and, thus, a major health problem. A variety of environmental factors including physical and chemical noxae, as well as pathogen infections could contribute to the development of gastric cancer. The transcription factor nuclear factor kappa B (NF-κB) and its dysregulation has a major impact on gastric carcinogenesis due to the regulation of cytokines/chemokines, growth factors, anti-apoptotic factors, cell cycle regulators, and metalloproteinases. Changes in NF-κB signaling are directed by genetic alterations in the transcription factors themselves, but also in NF-κB signaling molecules. NF-κB actively participates in the crosstalk of the cells in the tumor micromilieu with divergent effects on the heterogeneous tumor cell and immune cell populations. Thus, the benefits/consequences of therapeutic targeting of NF-κB have to be carefully evaluated. In this review, we address recent knowledge about the mechanisms and consequences of NF-κB dysregulation in gastric cancer development and therapy.

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“…In 2017, Karamanakos’ groups treated a GBM patient with DSF in combination with the standard of care and improved progression-free and overall survival [ 28 ]. Although DSF has been suggested as an anti-tumor agent [ 40 , 41 , 42 ], and a phase II clinical trial indicated that DSF is safe and is well-tolerated, combining TMZ and DSF did not significantly improve the prognosis of recurrent GBM patients [ 43 ]. In addition, various studies have indicated that DSF may be a good sensitizer for radio- and chemotherapy [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Disulfiram Sensitizes a Therapeutic-Resistant Glioblastoma to the TGF-β Receptor Inhibitor

Liu

Lin

et al. 2021

IJMS

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Despite neurosurgery following radiation and chemotherapy, residual glioblastoma (GBM) cells develop therapeutic resistance (TR) leading to recurrence. The GBM heterogeneity confers TR. Therefore, an effective strategy must target cancer stem cells (CSCs) and other malignant cancer cells. TGF-β and mesenchymal transition are the indicators for poor prognoses. The activity of aldehyde dehydrogenases (ALDHs) is a functional CSC marker. However, the interplay between TGF-β and ALDHs remains unclear. We developed radiation-resistant and radiation-temozolomide-resistant GBM models to investigate the underlying mechanisms conferring TR. Galunisertib is a drug targeting TGF-β receptors. Disulfiram (DSF) is an anti-alcoholism drug which functions by inhibiting ALDHs. The anti-tumor effects of combining DSF and Galunisertib were evaluated by in vitro cell grow, wound healing, Transwell assays, and in vivo orthotopic GBM model. Mesenchymal-like phenotype was facilitated by TGF-β in TR GBM. Additionally, TR activated ALDHs. DSF inhibited TR-induced cell migration and tumor sphere formation. However, DSF did not affect the tumor growth in vivo. Spectacularly, DSF sensitized TR GBM to Galunisertib both in vitro and in vivo. ALDH activity positively correlated with TGF-β-induced mesenchymal properties in TR GBM. CSCs and mesenchymal-like GBM cells targeted together by combining DSF and Galunisertib may be a good therapeutic strategy for recurrent GBM patients.

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The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways

Cited by 15 publications

References 24 publications

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

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

NF-κB in Gastric Cancer Development and Therapy

Disulfiram Sensitizes a Therapeutic-Resistant Glioblastoma to the TGF-β Receptor Inhibitor

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