Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer

被引：23

作者：

Yang, Xu ^{[1
,2
]}

Deng, Li ^{[3
]}

Diao, Xianhong ^{[1
,2
]}

Yang, Siyuan ^{[3
]}

Zou, Li ^{[1
]}

Yang, Qin ^{[1
]}

Li, Jian ^{[4
]}

Nie, Jianyun ^{[3
]}

Zhao, Lina ^{[1
]}

Jiao, Baowei ^{[1
,5
]}

机构：

[1] Chinese Acad Sci, Kunming Inst Zool, Natl Key Lab Genet Evolut & Anim Models, Kunming 650201, Yunnan, Peoples R China

[2] Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650201, Peoples R China

[3] Kunming Med Univ, Affiliated Hosp 3, Dept Breast Canc, 519 Kunzhou Rd, Kunming 650118, Yunnan, Peoples R China

[4] Chinese Acad Sci, Inst Ctr Shared Technol & Facil, Kunming Inst Zool, Kunming 650201, Yunnan, Peoples R China

[5] Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common D, Kunming 650203, Yunnan, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 11期

基金：

中国国家自然科学基金;

关键词：

CELL-DEATH; OXIDATIVE STRESS; STEM-CELLS; COPPER; MECHANISM; STATISTICS; EXPRESSION; APOPTOSIS; COMPLEX; GROWTH;

D O I：

10.1016/j.isci.2023.108218

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：19