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First Page

1560

Last Page

1572

Abstract

Background/purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: MM1 suppresses OSCC progression through coordinated inhibition of c-MYC associated oncogenic pathways and represents a promising candidate for further preclinical development.

Publication Date

2026

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