Identification of a novel EphB4 inhibitor, Sanguinarine, which attenuates β-catenin signaling to inhibit tumor proliferation and migration in lung cancer - PubMed
3 hours ago
- #Lung Cancer
- #EphB4
- #Sanguinarine
- EphB4, a receptor tyrosine kinase, promotes tumor growth and is a potential therapeutic target in lung cancer (LC).
- Sanguinarine (Sang) was identified as a novel EphB4 inhibitor with high binding affinity.
- Sang inhibits LC cell proliferation, migration, and invasion by targeting EphB4.
- Mechanistically, Sang binds to EphB4, inhibiting its phosphorylation and disrupting interaction with β-catenin.
- Sang increases β-catenin phosphorylation, ubiquitination, and proteasomal degradation, suppressing EMT and tumor progression.
- Sang also disrupts IGF-II-mediated EphB4 stabilization, leading to its polyubiquitination and degradation.
- In vivo, Sang reduces tumor volume and mass in LC xenograft models without significant toxicity.
- Findings suggest Sang as a promising clinical candidate for LC treatment, warranting further clinical trials.