Lycobetaine Has Therapeutic Efficacy in Lung Squamous Cell Carcinoma by Targeting USP32 to Trigger Ferroptosis.

ABSTRACT: Ubiquitin-specific protease 32 (USP32), a deubiquitylating enzyme that controls the ubiquitin process, is overexpressed in multiple cancers and serves as a promising therapeutic target for cancer therapy. Drugs targeting ferroptosis have exhibited promising anticancer activity. Lycobetaine (LBT), a natural alkaloid, holds promise against various cancers, yet its specific targets and anticancer mechanisms remain unclear. In this study, we show that LBT induced ferroptosis in lung squamous cell carcinoma (LUSC) cells, accompanied by glutathione depletion and the accumulation of lipid peroxidation, malondialdehyde, and ferrous iron. Mechanistically, drug affinity responsive target stability-based mass spectrometry analysis, molecular dynamics simulations, and a cellular thermal shift assay co

SUBMITTER: Xing S 

PROVIDER: S-EPMC11941616 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature