Robinetin inhibits osteosarcoma proliferation and migration, acting via the Slug/Twist signaling axis

Osteosarcoma is the most common primary malignant bone tumor, predominantly affecting young individuals. Despite standard chemotherapy and surgical resection, the overall survival rate has reached a plateau, emphasizing the need for more effective treatments. Flavonoids are antioxidant molecules with recognized anti-inflammatory and anticancer properties. In this study, we aimed to investigate the therapeutic potential of five flavonoids against four different osteosarcoma cell lines (MG-63, Saos-2 HOS, and 143B). Among the five structurally different flavonoids, robinetin exhibited the highest toxicity against osteosarcoma cells while sparing healthy human lung fibroblasts (MRC-5). Robinetin synergized with doxorubicin, reducing 143B cell viability, delaying migration, and downregulating metastasis-related transcription factors c-Jun, Snail, Slug, and Twist2. In vivo, robinetin inhibited the growth of osteosarcoma tumor xenografts in a chick chorioallantoic membrane model. Our study highlights and reports for the first time the therapeutic value of robinetin and demonstrates the potential of robinetin in osteosarcoma treatment.