RNA sequencing of osteosarcoma cells treated with salinomycin and its thiourea derivatives
Osteosarcoma stem cells (OSCs) drive metastasis, chemoresistance, and recurrence in osteosarcoma. Salinomycin exhibits potent anti-OSC activity but has a narrow therapeutic window. We designed 19 salinomycin C-20 thiourea derivatives and applied a multidimensional screening strategy with an OSC spheroid model. A novel compound SAL3 exhibits significantly enhanced OSC-killing potency and stemness-suppression capacity. Mechanistically, SAL3 eliminated OSCs by promoting ferroptosis through iron chelation and lipid peroxidation pathways, induced mitochondrial dysfunction, and downregulated Wnt/beta-catenin signaling via enhanced phosphorylation of GSK3beta at Tyr216. RNA-seq was performed on 143b OSCs treated with SAL or SAL3 to investigate transcriptomic changes.