Artocarpin, an isoprenyl flavonoid, induced apoptosis and inhibited cell migration in osteosarcoma

抄録

Osteosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Osteosarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The use of combination chemotherapy and surgery enables long-term survival in approximately 60-70% of cases. However, the necessity for surgery, the poor prognosis of patients with metastatic or recurrent disease, and the lack of establishment of second-line chemotherapy suggest that improvements in chemotherapy are desperately needed.

Artocarpin, a prenylated flavonoid purified from the plant Artocarpus communis, has been reported to have anti-inflammation and anti-cancer properties. However, the effect of Artocarpin on cell migration and apoptosis in human osteosarcoma cells is mostly unknown. Here, we found that Artocarpin induced apoptosis and autophagy of osteosarcoma cancer cells at high concentrations, but Artocarpin did not induce cell apoptosis in human normal bone cell (hFOB 1.19). Artocarpin induced the clustering of mitochondria to go around the nuclei, and then to loss mitochondrial membrane potential. In additional, we found that Artocarpin reduced the cell migration and invasion of osteosarcoma cancer cells at noncytotoxic concentrations. MMPs are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. We also found that incubation of osteosarcoma cells with Artocarpin reduced mRNA transcription for, and cell surface expression.

These results will help us to understand the mechanism of Artocarpin in osteosarcoma, and be beneficial for the development of effective anti-osteosarcoma drugs.