Magnolol Suppresses Osteosarcoma Progression via Apoptosis Induction and EGFR/AKT Pathway Inactivation in a U-2 OS Xenograft Model

Abstract

Background/aim: Osteosarcoma is a primary malignant bone tumor with poor prognosis due to frequent metastasis and limited response to standard therapies.

Materials and methods: This study investigated the antitumor effects of magnolol, a bioactive compound from Magnolia officinalis, using a U-2 OS xenograft mouse model. Mice received oral magnolol (40 or 60 mg/kg/day) for 14 days. Tumor volume, histology, serum biochemistry, and immunohistochemistry were analyzed.

Results: Magnolol significantly delayed tumor progression in a dose-dependent manner without inducing systemic toxicity. Serum aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (γ-GT), and creatinine (CREA) levels, along with hematoxylin and eosin stain (H&E) staining of major organs, indicated no hepatic or renal injury. Mechanistically, magnolol up-regulated cleaved caspase-3/8/9, BAX, and BAK while down-regulating Bcl-2 and C-FLIP. Furthermore, magnolol suppressed phosphorylation of EGFR and AKT and reduced expression of Cyclin D1, MMP-9, and VEGF-A.

Conclusion: Magnolol exerts potent anti-osteosarcoma effects by inducing apoptosis and inhibiting the EGFR/AKT signaling pathway, supporting its potential as a safe adjunctive therapy.

Keywords: AKT; EGFR; Magnolol; apoptosis; osteosarcoma.