sakuranin targets lung cancer: in vitro, in vivo, and in silico analysis

Lung cancer (lc), a prominent cause of cancer-related mortality globally, necessitates innovative therapies with strong pharmacokinetics. this study evaluated the anticancer potential of sakuranin in a549 lc cells and a xenograft model, focusing on cytotoxicity, pro-oxidative, apoptotic, anti-metastatic, and cell cycle arrest effects, alongside molecular interactions with pi3k/akt/mtor pathway proteins. the physicochemical properties and absorption, distribution, metabolism, excretion (adme)/toxicity profile were analyzed via swissadme and protox-3.0. cytotoxicity was assessed via mtt assay, reactive-oxygen-species (ros) using dichloro-dihydro-fluorescein-diacetate (dcfh-da) fluorescence, mitochondrial membrane potential (mmp) via rhodamine (rh)-123 staining, apoptosis via 4’,6-diamidino-2-phenylindole (dapi)-based nuclear morphology, and cell cycle arrest via flow cytometry. anti-migratory/invasive effects were tested using transwell assays. in vivo efficacy was observed in a xenograft model, and molecular docking evaluated binding interactions to pi3k/akt/mtor proteins. sakuranin complied with lipinski’s rules, demonstrating favorable solubility and bioavailability. it exhibited dose-dependent cytotoxicity in a549 cells (ic₅₀: 74.22 µg/ml; 82% viability reduction at the highest dose). ros levels tripled, while mmp depolarization reduced fluorescence intensity by 59%. apoptotic nuclear changes were observed, and cell cycle analysis revealed 70% g2/m phase arrest. migration and invasion decreased by 70% and 65%, respectively. in vivo, a 200 mg/kg dose resulted in a 90% drop in tumor volume and a 72% drop in tumor weight. molecular docking studies confirmed strong interactions of sakuranin with pi3k (-9.2 kcal/mol), akt (-10.5 kcal/mol), mtor (-8.7 kcal/mol), and erk (-8.1 kcal/mol), suggesting its role in modulating the pi3k/akt/mtor signaling cascade. conclusion: sakuranin demonstrates potent cytotoxic, pro-apoptotic, and anti-metastatic effects in lc models. its interaction with key signaling proteins underscores its therapeutic potential. these findings advocate further exploration of sakuranin as a promising lc treatment candidate targeting the pi3k/akt/mtor axis.