The novel isoflavone 7-hydroxy-3′,4′-benzoisoflavone induces cell apoptosis in human osteosarcoma cells
Journal
Cancer Letters
Journal Volume
271
Journal Issue
1
Pages
117-128
Date Issued
2008
Author(s)
Abstract
Osteosarcoma is the most frequent primitive malignant tumor of the skeletal system and is characterized by an extremely aggressive clinical course that lacks an effective treatment. This study is the first to investigate the anti-cancer effects of a new isoflavone-derived 7-hydroxy-3′,4′-benzoisoflavone (HBI) in human osteosarcoma cells. HBI-induced cell apoptosis in human osteosarcoma cell lines. The accumulation of reactive oxygen species (ROS) is a critical mediator in HBI induced cell death. HBI also induced apoptosis signal-regulating kinase 1 (ASK1) dephosphorylation, p38, JNK and p53 phosphorylation. Transfection with ASK1, p38 and JNK small interfering RNA (siRNA) antagonized HBI-induced cell apoptosis. HBI also triggered the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl2 ratio. Bax knockdown using a Bax siRNA strategy reduced Bax expression and subsequent cell death. In addition, ASK1, p38 and JNK siRNA reduced HBI-induced p53 phosphorylation and Bax expression. These results suggest that the ROS-ASK1-p38/JNK-p53 and Bax pathway plays a critical role in HBI's anti-cancer effects. ? 2008 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
7 hydroxy 3',4' benzoisoflavone; alpha tubulin; apoptosis signal regulating kinase 1; catalase; cytochrome c; isoflavone derivative; protein Bax; protein bcl 2; protein p53; reactive oxygen metabolite; small interfering RNA; stress activated protein kinase; synaptophysin; unclassified drug; animal cell; antineoplastic activity; apoptosis; article; cancer cell culture; controlled study; human; human cell; mitochondrion; mouse; nonhuman; osteosarcoma cell; priority journal; protein dephosphorylation; protein expression; protein phosphorylation; Apoptosis; Cell Line, Tumor; Enzyme Activation; Flow Cytometry; Humans; In Situ Nick-End Labeling; Isoflavones; MAP Kinase Kinase 4; MAP Kinase Kinase Kinase 5; Osteosarcoma; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Reactive Oxygen Species; Signal Transduction
Type
journal article