KMID : 1140120110160030269
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Cancer Prevention Research 2011 Volume.16 No. 3 p.269 ~ p.279
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Induction of Apoptosis by Ethanol Extract of Nerium indicum Stem Is Associated with Activation of JNK in Human Renal Carcinoma Caki-1 Cells
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Song Su-Jin
Kim Cheng-Yun Choi Yung-Hyun Hwang Won-Deok
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Abstract
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Nerium indicum Mill. is a medium-size evergreen flowering tree, widely distributed in Asia and used as traditional medicine. N. indicum is also one of the most poisonous plants, however it is reported that this plant extracts possess many pharmacological activities, including stimulating cardiac muscle, anti-diabetes, anti-angiogenesis and neuroprotection activities. In the present study, it was examined the biochemical mechanisms of apoptosis by ethanol extract of N. indicum stem (ENIS) in Caki-1 human renal carcinoma cells. Our data indicated that ENIS could inhibit the cell proliferation in a concentrationand time-dependent manners, which was connected with apoptosis induction as measured by DAPI staining and flow cytometry analysis. The induction of apoptosis by ENIS was associated with a loss of mitochondrial membrane potential (MMP), proteolytic activation of caspase-9 and caspase-3, and concomitant degradation of poly (ADP-ribose) polymerase (PARP) in Caki-1 cells. However, ENIS did not affect the activity of caspase-8. In addition, following exposure to ENIS, the activation of Jun N-terminal kinase (JNK) were concentration-dependently increased, and inhibition of JNK activation by pJNK inhibitor, SP600125, attenuated ENIS-induced apoptosis. Following exposure to ENIS, the generation of reactive oxygen species (ROS) were also increased, however inhibition of ROS generation by ROS scavenger, N-acetylcysteine (NAC), did not attenuat ENIS-induced apoptosis. Taken together, the results indicated that ENIS may be a potential chemotherapeutic agent for use in control of Caki-1 human renal carcinoma cell growth, and further studies will be needed for identification of active compounds that confer the anti-cancer activity of N. indicum extracts.
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KEYWORD
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Nerium indicum, Apoptosis, JNK, Caki-1
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