Caspase-independent death of human osteosarcoma cells by flavonoids is driven by p53-mediated mitochondrial stress and nuclear translocation of AIF and endonuclease G

被引:0
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作者
Sung-Ho Kook
Young-Ok Son
Song-Woo Chung
Seung-Ah Lee
Jong-Ghee Kim
Young-Mi Jeon
Jeong-Chae Lee
机构
[1] Institute of Oral Bioscience,Laboratory of Cell Biology in Department of Orthodontics
[2] Chonbuk National University,Division of Biological Sciences
[3] Chonbuk National University,Department of Nursing
[4] Chonnam Techno College,Research Center of Bioactive Materials
[5] Chonbuk National University,undefined
来源
Apoptosis | 2007年 / 12卷
关键词
Flavonoid; HOS cells; Apoptosis; p53; Mitochondrial apoptogenic factor;
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摘要
Flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine that has long been used in Korea as both a food additive and antitumor agent. It was previous reported that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), inhibited the proliferation and induced apoptosis in human osteosarcoma (HOS) cells. This study examined the mechanisms involved in the RCMF-mediated apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis in HOS cells by inducing p53 in the cells resulting in the decrease in Bcl-2 level, activation of Bax, and cytoplasmic release of cytochrome c, which led to the translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) into the nucleus. However, the RCMF-induced apoptosis was suppressed by transfecting the cells with antisense p53 oligonucleotides but not by treating them with a MAPK or caspase inhibitor. This suppression occurred through the regulation of Bcl-2 members as well as by preventing the nuclear translocation of the mitochondrial apoptogenic factors. Overall, it appears that p53-mediated mitochondrial stress and the nuclear translocation of AIF and EndoG are mainly required for the apoptosis induced by RCMF.
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页码:1289 / 1298
页数:9
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