Anticancer effects of disulfiram in T-cell malignancies through NPL4-mediated ubiquitin–proteasome pathway

Autor: Cunte Chen, Dingrui Nie, Youxue Huang, Xibao Yu, Zheng Chen, Mengjun Zhong, Xin Liu, Xianfeng Wang, Songnan Sui, Zhuandi Liu, Jiaxiong Tan, Zhi Yu, Yangqiu Li, Chengwu Zeng
Rok vydání: 2022
Předmět:
Zdroj: Journal of Leukocyte Biology. 112:919-929
ISSN: 1938-3673
0741-5400
DOI: 10.1002/jlb.5ma1121-644r
Popis: T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma (TCL), are characterized by inferior treatment effects, high heterogeneity, poor prognosis, and a lack of specific therapeutic targets and drugs to improve outcome. Disulfiram (DSF) is a drug used to clinically control alcoholism that has recently been shown to be cytotoxic for multiple cancers. However, the underlying effects and mechanisms of DFS treatment in patients with T-cell malignancies are not well characterized. In this study, we report that DSF promotes apoptosis and inhibits the proliferation of malignant T-cell cell lines and primary T-ALL cells. We provide evidence that DSF exerts anticancer activity in T-cell malignancies by targeting the NPL4-mediated ubiquitin–proteasome pathway. Notably, high expression of NPL4 and 2 ubiquitin–proteasome pathway genes, anaphase-promoting complex subunit 1 (ANAPC1) and proteasome 26S subunit ubiquitin receptor, non-ATPase 2 (PSMD2), was significantly associated with unfavorable overall survival (OS) for patients with TCL and T-ALL (p
Databáze: OpenAIRE
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