Berberine Reduces the Metastasis of Chondrosarcoma by Modulating theαvβ3 Integrin and the PKCδ, c-Src, and AP-1 Signaling Pathways

Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis, especially to the lungs. Patients diagnosed with chondrosarcoma have poor prognosis. Berberine, an active component of the Ranunculaceae and Papaveraceae families of plant, has been proven to induce tumor apoptosis and to prevent the metastasis of cancer cells. However, the effects of berberine in human chondrosarcoma are largely unknown. In this study, we found that berberine did not induce cell apoptosis in human primary chondrocytes and chondrosarcoma cells. However, at noncytotoxic concentrations, berberine reduced the migration and invasion of chondrosarcoma cancer cells. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. We also found that incubation of chondrosarcoma cells with berberine reduced mRNA transcription for, and cell surface expression of, the α v β 3 integrin, with additional inhibitory effects on PKC δ , c-Src, and NF- κ B activation. Thus, berberine may be a novel antimetastasis agent for the treatment of metastatic chondrosarcoma.