Schisantherin A induces ferroptosis in non‑small cell lung cancer through activation of the YAP/ACSL4/TfR signaling pathway.

Schisantherin A (Sch A), a compound derived from , has anti‑inflammatory, antitumor, neuroprotective and antifibrotic properties. However, to the best of our knowledge, the role of Sch A in non‑small cell lung cancer (NSCLC) has not yet been reported. The purpose of the present study was to determine whether Sch A can prevent the development of NSCLC and to elucidate the underlying mechanisms involved. The results of the present study demonstrated that Sch A inhibited the viability of A549 and HCC827 cells. Furthermore, Sch A increased the intracellular Fe level, reduced the mitochondrial membrane potential and depleted the glutathione content in lung cancer cells. These effects were reversed by the ferroptosis inhibitors ferrostatin‑1 and deferoxamine. Bioinformatics analysis and reverse transcription‑quantitative PCR results suggested that Sch A increased the mRNA levels of the transcription factor yes‑associated protein (YAP). Additionally, Sch A upregulated the expression of YAP and ferroptosis‑related proteins, including acyl‑CoA synthase long‑chain family member 4 (ACSL4) and transferrin receptor (TfR), in lung cancer cells. Silencing of YAP led to the downregulation of its downstream targets, ACSL4 and TfR, even in the presence of Sch A. , Sch A significantly inhibited subcutaneous tumor growth in nude mice. In conclusion, Sch A may activate the YAP/ACSL4/TfR signaling axis to induce ferroptosis in NSCLC cells, positioning it as a potential small‑molecule therapeutic agent for NSCLC.