Diallyl disulfide suppresses FOXM1-mediated proliferation and invasion in osteosarcoma by upregulating miR-134

Area of Science:

• Oncology
• Molecular Biology
• Natural Products Chemistry

Background:

• Osteosarcoma (OS) remains a significant challenge in orthopedic oncology.
• Diallyl disulfide (DADS), a garlic-derived compound, exhibits known anticancer properties.
• The specific effects of DADS on osteosarcoma have not been previously investigated.

Purpose of the Study:

• To investigate the anticancer potential of DADS in osteosarcoma.
• To elucidate the underlying molecular mechanisms of DADS's action in OS cells.
• To explore the role of miR-134 in mediating DADS's effects.

Main Methods:

• Cell viability assays (MTT) were performed on OS cell lines.
• Quantitative real-time PCR (qRT-PCR) was used to measure miR-134 expression.
• In vitro functional assays assessed cell proliferation and invasion.
• Bioinformatics analysis predicted miR-134 targets.
• Western blotting analyzed protein expression levels.
• In vivo xenograft models evaluated antitumor activity.

Main Results:

• DADS reduced OS cell viability and inhibited proliferation and invasion in a dose- and time-dependent manner.
• DADS significantly upregulated miR-134 expression in OS cells and xenograft tumors.
• Downregulation of miR-134 partially reversed the anti-proliferative and anti-invasive effects of DADS.
• Bioinformatics and luciferase assays confirmed FOXM1 as a direct target of miR-134.
• DADS inhibited FOXM1 expression, which was linked to its antiproliferative and anti-invasive effects.
• DADS modulated the expression of cell cycle regulators, including downregulation of cyclin D1, c-myc, and LEF1, and upregulation of p21.

Conclusions:

• Diallyl disulfide (DADS) demonstrates significant anticancer activity against osteosarcoma.
• The mechanism involves the upregulation of miR-134, leading to the inhibition of FOXM1 expression.
• DADS exhibits promising therapeutic potential for osteosarcoma treatment.