2-O-Methylmagnolol suppresses oral squamous cell carcinoma progression by targeting c-MYC signaling.

Oral squamous cell carcinoma (OSCC) is characterized by aggressive growth and frequent recurrence, highlighting the need for novel targeted therapies. Magnolol, a bioactive compound derived from Magnolia officinalis, exhibits anti-tumor activity. In this study, we synthesized a methoxylated derivative, 2-O-methylmagnolol (MM1), and evaluated the anti-OSCC efficacy and underlying mechanisms of magnolol and MM1. Human OSCC cell lines (SAS and OECM1) were treated with magnolol or MM1. Cell proliferation, migration, and invasion were analyzed using functional assays. Cell-cycle distribution and apoptosis were assessed by flow cytometry and DiOC6/PI staining. Protein expression of c-MYC and downstream regulators was examined by Western blotting. Anti-tumor efficacy was further evaluated in a xenograft mouse model. Both magnolol and MM1 significantly inhibited OSCC cell proliferation, migration, and invasion, and induced G1-phase arrest and apoptosis. MM1 consistently demonstrated greater anti-tumor potency than magnolol. Mechanistically, both compounds downregulated c-MYC protein expression, accompanied by increased p21 and decreased CDC25A, CDK4, and Cyclin D1 levels, resulting in G1-S cell-cycle blockade. Epithelial-mesenchymal transition (EMT)-associated proteins were also suppressed, consistent with reduced migratory and invasive capacity. In vivo, MM1 produced stronger tumor growth inhibition without evident systemic toxicity. MM1 suppresses OSCC progression through coordinated inhibition of c-MYC associated oncogenic pathways and represents a promising candidate for further preclinical development.