4′-hydroxywogonin inhibits oral squamous cell carcinoma progression by targeting Gas6/Axl signaling axis

Background/purpose: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck malignancies, with current therapeutic strategies often limited by low efficacy and drug resistance. In this study, we investigated the anticancer potential and underlying mechanisms of 4′-hydroxywogonin, a flavonoid extracted from Scutellaria baicalensis, in OSCC. Materials and methods: OSCC cell lines were treated with 4′-hydroxywogonin, and its anticancer effects were evaluated using cell functional assays. Western blot analysis was performed to examine the regulatory pathways involved, and rescue assays were conducted to validate its mechanism of action. Results: 4′-Hydroxywogonin selectively inhibited OSCC cell proliferation, migration, and invasion without inducing cytotoxicity in normal human cells. Mechanistic studies revealed that 4′-hydroxywogonin downregulated Axl and its ligand Gas6, leading to the suppression of PI3K/AKT signaling, cell cycle checkpoint regulation, and epithelial–mesenchymal transition (EMT)-related proteins, ultimately inducing G1 phase cell cycle arrest and apoptosis. Moreover, the combination of 4′-hydroxywogonin with cisplatin significantly enhanced its inhibitory effects on OSCC. Conclusion: 4′-Hydroxywogonin exhibits potential as a novel therapeutic agent for OSCC, with the capacity to enhance cisplatin-mediated anticancer effects, highlighting its potential in combination therapy.