a-rhodopsin-transport-assay-by-high-content-imaging-analysis

A Rhodopsin Transport Assay by High-Content Imaging Analysis

Rhodopsin misfolding mutations lead to rod photoreceptor death that is manifested as autosomal dominant retinitis pigmentosa (RP), a progressive blinding ...

distribution-traditional-chinese-medicine-pattern-elements-patients

Distribution of Traditional Chinese Medicine Pattern Elements in Patients with Gastric Cancer: A Cross-Sectional Study

Gastric cancer remains a major cause of morbidity and mortality worldwide, with a particularly high burden in China. Traditional Chinese Medicine (TCM) ...

University of Pittsburgh

Wuxi No.2 Chinese Medicine Hospital

Alantolactone (ALT), a natural sesquiterpene lactone from Inula helenium L., demonstrates potent antitumor activity in various human cancers, notably non-small cell lung cancer (NSCLC). Despite its recognized efficacy, the precise mechanisms of action remain elusive. Our study aimed to elucidate ALT's impact on NSCLC. Our findings suggested that ALT triggered apoptosis both in vitro and in vivo, underscoring its anticancer potential. Interestingly, the ferroptosis inhibitor (Fer-1), rather than necrostatin-1 (Nec-1) or Z-VAD-FMK, rescued ALT-induced cell death, implicating ferroptosis as pivotal. Subsequent analyses revealed ferroptosis as the primary mechanism underlying ALT-induced NSCLC cell death, supported by markers including ROS accumulation, MDA elevation, GSH depletion, Fe generation, and GPX4 reduction. Through DARTS/MS proteomics, we identified FTH1 as the target of ALT-induced ferroptosis. Immunoblotting confirmed ALT's inhibition of FTH1 protein expression and accelerated its degradation in NSCLC cells. Immunoprecipitation assays demonstrated increased FTH1 ubiquitination induced by ALT. Additionally, ALT induced ferroptosis and facilitated Fe accumulation via FTH1 ubiquitination. Importantly, ALT displayed potent antitumor effects in a subcutaneous xenograft model in BALB/c-nu/nu nude mice by enhancing ferroptosis. In summary, ALT induced ferroptosis by promoting intracellular Fe accumulation through accelerated FTH1 degradation, highlighting its potential as an antitumor agent targeting ferroptosis.

ArticleTotal : 2	Year
Publication title Cited by 1	2019
Publication title	2025

Yuanyuan Chen

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