2. Academic Validation
  3. Bavachinin Suppresses Growth and Metastasis of Oral Squamous Cell Carcinoma through GSK-3β/β-Catenin Pathway: Potential for Synergistic Anticancer Therapy with Cisplatin

Bavachinin Suppresses Growth and Metastasis of Oral Squamous Cell Carcinoma through GSK-3β/β-Catenin Pathway: Potential for Synergistic Anticancer Therapy with Cisplatin

  • Biomed J. 2026 Apr 7:100975. doi: 10.1016/j.bj.2026.100975.
Pei-Yu Hsu 1,  Yann-Lii Leu 2,  Chin-Chuan Chen 2,  Min Chen 3,  Kai-Ping Chang 4,  Wan-Ling Wang 5,  Fei-Wen Jan 5,  Sien-Hung Yang 6,  Chia-Yu Yang 7
Affiliations

Affiliations

  • 1 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Division of Internal and Pediatric Chinese Medicine, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan City 333008, Taiwan (R.O.C.).
  • 2 Graduate Institute of Natural products, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Biobank, Chang Gung Memorial Hospital, Taoyuan City 333423, Taiwan (R.O.C.).
  • 3 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.).
  • 4 Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan City 333423, Taiwan (R.O.C.); School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Molecular Medicine Research Center, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.).
  • 5 Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.).
  • 6 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Division of Internal and Pediatric Chinese Medicine, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan City 333008, Taiwan (R.O.C.); School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.). Electronic address: [email protected].
  • 7 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.); Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan City 333423, Taiwan (R.O.C.); Molecular Medicine Research Center, Chang Gung University, Taoyuan City 333323, Taiwan (R.O.C.). Electronic address: [email protected].
PMID: 41956246 DOI: 10.1016/j.bj.2026.100975
Abstract

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis, often complicated by recurrence, metastasis, and chemoresistance. While cisplatin remains a cornerstone of OSCC treatment, its efficacy is limited by systemic toxicity and resistance. In search of safer, effective adjunctive strategies, we investigated bavachinin, a flavanone from Psoralea corylifolia L., for its antitumor potential in OSCC.

Materials and methods: Integrated in vitro, in silico, and in vivo approaches were employed. Functional assays evaluated cell viability, Apoptosis, migration, and invasion. Transcriptomic profiling identified dysregulated pathways, with key targets validated by quantitative Reverse transcription PCR (qRT-PCR). Molecular docking predicted protein targets, confirmed by Western blot. Toxicity and therapeutic efficacy were evaluated in C57BL/6 mice and OSCC cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.

Results: Bavachinin significantly reduced cell viability, induced G2/M phase arrest, promoted Apoptosis, and inhibited migration and invasion in OSCC cells. Transcriptomic profiling and qRT-PCR revealed suppression of genes involved in extracellular matrix remodeling and cell adhesion. Glycogen synthase kinase-3β (GSK-3β) was identified as a potential target by molecular docking analysis, confirmed by increased phosphorylation at Tyr216 and β-catenin degradation, leading to downregulation of matrix metalloproteinase-2 and fibronectin. As natural compounds are rarely used as monotherapies, bavachinin combined with cisplatin showed synergistic antitumor effects in OSCC CDX and PDX models, without systemic toxicity in mice.

Conclusion: Bavachinin exerts potent antitumor effects via modulation of the GSK-3β/β-catenin pathway and may serve as a promising adjunct to cisplatin in OSCC treatment.

Keywords

GSK-3β; bavachinin; cisplatin; metastasis; oral squamous cell carcinoma; traditional Chinese medicine.

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