Caspase-independent death of human osteosarcoma cells by flavonoids is driven by p53-mediated mitochondrial stress and nuclear translocation of AIF and endonuclease G |
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Authors: | Sung-Ho Kook Young-Ok Son Song-Woo Chung Seung-Ah Lee Jong-Ghee Kim Young-Mi Jeon Jeong-Chae Lee |
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Institution: | (1) Laboratory of Cell Biology in Department of Orthodontics, Institute of Oral Bioscience, Chonbuk National University, Chonju, 561-756, Korea;(2) Division of Biological Sciences, Chonbuk National University, Chonju, 561-756, Korea;(3) Department of Nursing, Chonnam Techno College, Chonnam, 516-911, Korea;(4) Research Center of Bioactive Materials, Chonbuk National University, Chonju, 561-756, Korea |
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Abstract: | 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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Keywords: | Flavonoid HOS cells Apoptosis p53 Mitochondrial apoptogenic factor |
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