The novel isoflavone 7-hydroxy-3',4'-benzoisoflavone induces cell apoptosis in human osteosarcoma cells.
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.
Hou
Chun-Han
CH
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
Fong
Yi-Chin
YC
Chen
Jung-Tsan
JT
Liu
Ju-Fang
JF
Lin
Min-Sheng
MS
Chang
Chih-Shiang
CS
Tang
Chih-Hsin
CH
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007529:Isoflavones / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C533094:7-hydroxy-3',4'-benzoisoflavone; D007529:Isoflavones; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D048670:MAP Kinase Kinase 4