Plant flavonoid taxifolin inhibits the growth, migration and invasion of human osteosarcoma cells

Abstract

The aim of the present study was to investigate the anti-cancer effects of the natural plant flavonoid, taxifolin, on human osteosarcoma cancer cells. Taxifolin was demonstrated to exhibit anti-cancer effects on U2OS and Saos-2 osteosarcoma cell lines. Treatment of cells with taxifolin inhibited proliferation and diminished colony formation in soft agar in a dose-dependent manner. In vivo, intraperitoneal administration of taxifolin in nude mice bearing U2OS xenograft tumors, significantly inhibited tumor growth. In addition, taxifolin treatment was demonstrated to promote G1 cell cycle arrest and cell apoptosis in U2OS and Saos-2 cell lines, as demonstrated by flow cytometry analysis. Western blot analysis demonstrated that taxifolin treatment was associated with a reduction in the expression levels of AKT serine/threonine kinase 1 (AKT), phosphorylated (p-Ser473) AKT, v-myc avian myelocytomatosis viral oncogene homolog (c-myc) and S-phase kinase associated protein 2 (SKP-2) in U2OS and Saos-2 cell lines. Overexpression of AKT considerably reversed the taxifolin-induced decrease in AKT, c-myc and SKP-2 protein expression and the decrease in AKT phosphorylation, suggesting that inactivation of AKT was a mediator of taxifolin-induced inhibition of c-myc and SKP-2. Furthermore, overexpression of SKP-2 in U2OS cells partially reversed the growth inhibition mediated by taxifolin. Finally, taxifolin treatment repressed cell migration and invasion in U2OS cells and this effect was markedly reversed by SKP-2 overexpression. The results of the present study indicate that taxifolin may present a potential novel therapeutic agent for osteosarcoma treatment.