A Cancer-Selective Zinc Ionophore Inspired by the Natural Product Naamidine A.

ABSTRACT: We present data demonstrating the natural product mimic, zinaamidole A (ZNA), is a modulator of metal ion homeostasis causing cancer-selective cell death by specifically inducing cellular Zn²⁺-uptake in transformed cells. ZNA's cancer selectivity was evaluated using metastatic, patient-derived breast cancer cells, established human breast cancer cell lines, and three-dimensional organoid models derived from normal and transformed mouse mammary glands. Structural analysis of ZNA demonstrated that the compound interacts with zinc through the N²-acyl-2-aminoimidazole core. Combination treatment with ZnSO₄ strongly potentiated ZNA's cancer-specific cell death mechanism, an effect that was not observed with other transition metals. We show that Zn²⁺-d

SUBMITTER: Vaden RM 

PROVIDER: S-EPMC8489793 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature