The novel isoflavone 7-hydroxy-3′,4′-benzoisoflavone induces cell apoptosis in human osteosarcoma cells

Chun Han Hou, Yi Chin Fong, Jung Tsan Chen, Ju Fang Liu, Min Sheng Lin, Chih Shiang Chang, Chih Hsin Tang

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)117-128
Number of pages12
JournalCancer Letters
Volume271
Issue number1
DOIs
Publication statusPublished - Nov 18 2008

Keywords

  • ASK1
  • Isoflavone
  • JNK
  • Osteosarcoma
  • P38

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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