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Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer.

Published:16 October 2023 DOI: 10.1016/j.isci.2023.108218 PMID: 37953954
Xu Yang,?Li Deng,?Xianhong Diao,?Siyuan Yang,?Li Zou,?Qin Yang,?Jian Li,?Jianyun Nie,?Lina Zhao,?Baowei Jiao

Abstract

Triple-negative breast cancer (TNBC) poses a considerable challenge due to its aggressive nature. Notably, metal ion-induced cell death, such as ferroptosis, has garnered significant attention and demonstrated potential implications for cancer. Recently, cuproptosis, a potent cell death pathway reliant on copper, has been identified. However, whether cuproptosis can be targeted for cancer treatment remains uncertain. Here, we screened the US Food and Drug Administration (FDA)-approved drug library and identified zinc pyrithione (ZnPT) as a compound that significantly inhibited TNBC progression. RNA sequencing revealed that ZnPT disrupted copper homeostasis. Furthermore, ZnPT facilitated the oligomerization of dihydrolipoamide S-acetyltransferase, a landmark molecule of cuproptosis. Clinically, high expression levels of cuproptosis-related proteins were significantly correlated with poor prognosis in TNBC patients. Collectively, these findings indicate that ZnPT can induce cell death by targeting and disrupting copper homeostasis, providing a potential experimental foundation for exploring cuproptosis as a target in drug discovery for TNBC patients.

Substances (5)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Zinc pyrithione 13463-41-7 C10H8N2O2S2Zn 664 suppliers $5.00-$1010.61
RIPA buffer (5X) 6 suppliers $63.30-$109.00

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