Integrative chemoproteomics reveals anticancer mechanisms of silver(i) targeting the proteasome regulatory complex.

ABSTRACT: Silver compounds have favorable properties as promising anticancer drug candidates, such as low side effects, anti-inflammatory properties, and high potential to overcome drug resistance. However, the exact mechanism by which Ag(i) confers anticancer activity remains unclear, which hinders further development of anticancer applications of silver compounds. Here, we combine thermal proteome profiling, cysteine profiling, and ubiquitome profiling to study the molecular mechanisms of silver(i) complexes supported by non-toxic thiourea (TU) ligands. Through the formation of AgTU complexes, TU ligands deliver Ag⁺ ions to cancer cells and tumour xenografts to elicit inhibitory potency. Our chemical proteomics studies show that AgTU acts on the ubiquitin-proteasome system (UPS) and dis

SUBMITTER: Shao X 

PROVIDER: S-EPMC10988589 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature