Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer

Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer

Blog Article

Lighters Summary: 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 Pin 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.