Daidzin improves the cisplatin chemosensitivity for osteosarcoma via binding to β-catenin protein and suppressing the...

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• Osteosarcoma (OS) presents significant treatment challenges, particularly in pediatric and adolescent populations, due to chemotherapy resistance and poor outcomes.
• Natural products are increasingly recognized for their anticancer potential and translational value in drug development.
• Daidzin, a known bioactive compound, has demonstrated various biological activities, prompting investigation into its efficacy against OS.

Purpose of the Study:

• To investigate the therapeutic potential of daidzin as a treatment for osteosarcoma (OS).
• To evaluate the synergistic effects of daidzin in combination with cisplatin, a standard OS chemotherapeutic agent.
• To elucidate the underlying molecular mechanisms by which daidzin exerts its anti-OS effects.

Main Methods:

• In vitro cell-based assays and in vivo studies were conducted to assess daidzin's effects on OS cell proliferation, migration, and invasion.
• Combination treatments of daidzin and cisplatin were evaluated for their impact on OS cell viability and apoptosis.
• Molecular mechanisms were explored through analysis of beta-catenin (β-catenin) expression, Wnt pathway activity, molecular docking, thermal shift assay, and microscale thermophoresis (MST) assay.

Main Results:

• Daidzin significantly inhibited OS cell proliferation and metastasis in both cell-based and in vivo models.
• Combined treatment with daidzin and cisplatin demonstrated superior suppression of OS cell viability, migration, invasion, and enhanced apoptosis compared to single treatments.
• Daidzin was found to downregulate β-catenin protein levels and inhibit the Wnt pathway by reducing β-catenin protein stability, independent of transcriptional regulation.

Conclusions:

• Daidzin exhibits significant anti-osteosarcoma activity, inhibiting proliferation and metastasis.
• Daidzin acts as a potent adjuvant when combined with cisplatin, improving therapeutic outcomes and inducing apoptosis in OS.
• The therapeutic effect of daidzin is mediated through the destabilization of β-catenin protein, highlighting its potential as an adjuvant therapy for osteosarcoma.