Juglone targets CBS to inhibit the Wnt/β-catenin pathway and promotes osteosarcoma cell apoptosis

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Osteosarcoma (OS) presents significant treatment challenges due to toxicity and metastasis.
• Current therapies for OS have limited efficacy, especially against metastatic disease.
• Identifying novel therapeutic targets is crucial for improving OS patient outcomes.

Purpose of the Study:

• To identify critical oncogenes in osteosarcoma (OS) using bioinformatics.
• To investigate the role of cystathionine beta-synthase (CBS) in OS.
• To evaluate juglone as a potential therapeutic agent targeting CBS in OS.

Main Methods:

• Bioinformatic analysis to identify key genes in OS.
• In vitro experiments using OS cell lines (HOS, MG-63) to validate gene function.
• Drug screening using the HERB database to find natural inhibitors.
• In vivo studies in mouse models to assess therapeutic efficacy and toxicity.

Main Results:

• Bioinformatics identified cystathionine beta-synthase (CBS) as an oncogene linked to poor OS prognosis via the Wnt/β-catenin pathway.
• Juglone significantly inhibited OS cell proliferation, migration, invasion, and colony formation in vitro.
• Juglone treatment led to cell death, G2/M phase arrest, CBS degradation, and suppressed Wnt/β-catenin signaling.
• In vivo studies demonstrated juglone's efficacy in reducing tumor growth without observable toxicity.
• Clinical analysis confirmed CBS overexpression correlates with OS progression.

Conclusions:

• CBS is a critical oncogene in osteosarcoma, promoting tumor growth and metastasis.
• Juglone demonstrates potent anti-osteosarcoma activity by inhibiting CBS and the Wnt/β-catenin pathway.
• Juglone represents a promising, safe, and effective therapeutic candidate for osteosarcoma treatment.