5, 7-Dihydroxy-4′-methoxyisoflavone induces apoptosis by inhibiting the ERK and Akt pathways in human osteosarcoma cells. (February 2015)

• Record Type: Journal Article
• Authors: Lu, Xiaosheng; Zhao, Jinmin; Li, Tingyang; Huang, Meijing; Liang, Jian; Wei, Wen
• Is Part Of: Connective tissue research. Volume 56:Number 1(2015:Feb.)
• Page Start: 59
• Page End: 64
• Publication Date: 2015-02
• Subjects: Connective tissues -- Periodicals; 616.770072
• DOI: 10.3109/03008207.2014.984064
• Languages: English
• ISSNs: 0300-8207

Abstract

<abstract> <title>Abstract</title> <p>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.</p> </abstract>