Myricetin Inhibits Osteosarcoma Cell Viability and Modulates EMT-Related Genes Associated with the SNAI1/MMP-9 Axis

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• Osteosarcoma treatment is limited by metastasis and chemotherapy toxicity.
• Flavonoids, natural compounds, possess anticancer properties like antioxidant and anti-inflammatory effects.
• New therapeutic strategies are needed for osteosarcoma.

Purpose of the Study:

• Evaluate the anticancer potential of flavonoids in osteosarcoma.
• Investigate the synergistic effect of myricetin and doxorubicin.
• Explore the mechanism of action, including epithelial-mesenchymal transition (EMT) modulation.

Main Methods:

• Screened five flavonoids for cytotoxicity against osteosarcoma cell lines and fibroblasts.
• Assessed myricetin-doxorubicin interaction using a fixed-ratio combination.
• Evaluated cell migration, invasion, EMT markers (SNAI1, MMP9), and in vivo antitumor activity using a chick chorioallantoic membrane model.

Main Results:

• Myricetin demonstrated selective cytotoxicity against osteosarcoma cells.
• Myricetin synergized with doxorubicin, enhancing cytotoxicity and reducing cell migration.
• Myricetin downregulated SNAI1 and MMP9, indicating EMT pathway modulation.
• In vivo studies confirmed myricetin's antitumor activity.

Conclusions:

• Myricetin exhibits significant anticancer potential in osteosarcoma.
• Myricetin acts by inhibiting the SNAI1/MMP-9 signaling axis.
• Myricetin represents a promising therapeutic agent for osteosarcoma, potentially in combination with doxorubicin.