Ebracteolata cpd B causes ferroptosis and inhibits progression of lung adenocarcinoma

Objectives The study aims at examining the effects and mechanisms of E. ebracteolata containing serum and Ebracteolata cpd B on lung adenocarcinoma cells. Methods The medicated serum with E. ebracteolata was categorized into groups of low, medium, and high concentrations. The proliferative potential of A549 cells was evaluated through EdU assay and colony formation. To characterize the migratory and invasive capacities, scratch and Transwell tests were applied. Network analysis and molecular docking were employed to generate testable hypotheses by predicting potential targets of ECB for LUAD. The effect of ECB on the thermal stability of SRC protein was assessed using the cellular thermal shift assay. Evaluation of ECB’s Assessment of Drug-like Properties and Safety. The CCK-8 assay served for evaluating A549 and BEAS-2B cells viability. The influence of ECB on the process that A549 cells were proliferated, invaded and migrated was evaluated employing the above-mentioned experimental method. In vivo , a mouse lung cancer model was built to verify how ECB affected the A549 cells growth. The levels of ROS, MDA, GSH, and the content of Fe 2+ in A549 cells were measured. Observation of mitochondrial morphology by TEM. Western blot analysis assisted in measuring the expression of the proteins. Results Compared to the control group, the serum with E. ebracteolata dose-dependently reduced A549 cells’ proliferation, invasion, and migration. Network analysis identified 9 core targets from the potential targets. Molecular docking suggested that ECB could potentially interact with these core targets. ECB significantly increased the thermal stability of SRC. ECB demonstrates favorable oral bioavailability and a good safety profile. CCK-8 results indicated that ECB exerted no significant toxicity on BEAS-2B cells, whereas it inhibited the viability of A549 cells. At its IC 50 , ECB inhibited A549 cell proliferation, migration, and invasion, and induced ferroptosis. Notably, Fer-1 inhibited ECB-induced ferroptosis in A549 cells. These effects were verified by measuring ROS levels, GSH reduction, MDA elevation, and intracellular Fe 2+ content, and by TEM. GPX4 and SLC7A11 protein expression was reduced. Concurrently, ECB inhibited tumor-bearing mice’ relative tumor growth. Conclusion ECB suppresses A549 cells proliferation, invasion, and migration as well as promotes ferroptosis.