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5,7-Dihydroxy-4′-methoxyisoflavone induces apoptosis by inhibiting the ERK and Akt pathways in human osteosarcoma cells

Abstract Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. In this study we determine the effect of 5,7-dihydroxy-4′-methoxyisoflavone, a phytoestrogen, on proliferation and apoptosis in the human osteosarcoma (OS) cell line U2OS. 5,7-Dihydroxy-4′-methoxyisoflavone dose-dependently inhibited proliferation in U2OS cells, which was accompanied by an increase of early apoptotic cells. However, 5,7-dihydroxy-4′-methoxyisoflavone had little effect on the growth and apoptosis of normal human skin fibroblast (HSF) cells. This may indicate that 5,7-dihydroxy-4′-methoxyisoflavone can selectively inhibit the proliferation of cancerous cells. Meanwhile, 5,7-dihydroxy-4′-methoxyisoflavone decreased the protein levels of phosphorylated ERK and Akt. Inactivation of these pathways was confirmed by upregulation of Bax expression and downregulation of Bcl-2 expression. Phosphorylated Akt protein levels were decreased in HSF cells only at a high concentration (80 μM) of 5,7-dihydroxy-4′-methoxyisoflavone. Together, we suggest that 5,7-dihydroxy-4′-methoxyisoflavone promotes cell death of human OS cells U2OS by induction of apoptosis, which is associated with the inhibition of ERK and Akt signaling. Thus, 5,7-dihydroxy-4′-methoxyisoflavone may have less toxicity compared to normal tissue and could be a potential therapy for OS.