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KMID : 1140120110160020167
Cancer Prevention Research
2011 Volume.16 No. 2 p.167 ~ p.179
Induction of Apoptosis of Caki-1 Human Renal Carcinoma Cells by Ethanol Extract of Nerium indicum Leaf through Generation of Reactive Oxygen Species
Jang Ja-Won

Kim Cheng-Yun
Choi Yung-Hyun
Hwang Won-Deok
Abstract
Nerium indicum, an India-Pakistan-originated shrub belonging to the oleander family, is reported to possess many pharmacological activities including stimulation of cardiac muscle, anti-diabetes, anti-angiogenesis and neuroprotection activities. However, the cellular and molecular mechanisms of apoptosis induction by N. indicum extract in human cancer cells are poorly understood. In the present study, it was investigated the biochemical mechanisms of the pro-apoptotic effects by ethanol extract of N. indicum leaf (ENIL) in Caki-1 human renal carcinoma cells. It was found that ENIL could inhibit the cell proliferation of Caki-1 cells in a concentration- and time-dependent manner, which was associated with the induction of apoptosis as determined using DAPI staining and flow cytometric analysis. The induction of apoptotic cell death by ENIL was connected with a loss of mitochondrial membrane potential (MMP), proteolytic activation of caspase-3 and -9, and degradation of poly (ADP-ribose) polymerase (PARP) in Caki-1 cells. However, ENIL did not significantly affect the activity of caspase-8 and the levels of the inhibitor of apoptosis protein (IAP) family members. In addition, following exposure to ENIL, the production of reactive oxygen species (ROS) were increased, and inhibition of ROS generation by ROS scavenger, N-acetylcysteine (NAC), attenuated ENIL-induced apoptosis. Taken together, these findings suggest that ENIL may be a potential chemotherapeutic agent for use in control of Caki-1 human renal carcinoma cells and further studies will be needed for identification of active compounds that confer the anti-cancer activity of ENIL.
KEYWORD
Nerium indicum, Apoptosis, ROS, Caki-1
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