Discovery of Natural Resorcylic Acid Lactones as Novel Potent Copper Ionophores Covalently Targeting PRDX1 to Induce Cuproptosis for Triple-Negative Breast Cancer Therapy.

ABSTRACT: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Cuproptosis, a novel identified cell death form, is triggered by the direct binding of copper to lipoylated components of the tricarboxylic acid cycle. Identifying new effective drug targets and copper ionophores inducing cuproptosis for TNBC therapy is an urgent clinical need. In this study, a total of 24 resorcylic acid lactones (RALs, 1-24), including 9 previously unreported ones, were isolated from the endophyte Ilyonectria sp. Various assays demonstrated that pochonin D (16, PoD) effectively inhibited the proliferation of TNBC cells in vivo and in vitro. Further investigations, including transcriptomics, proteomics, bioinformatics analysis, CMap, OTTER, clini

SUBMITTER: Feng L 

PROVIDER: S-EPMC11869127 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature