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KMID : 0903520080510020129
Journal of the Korean Society of Agricultural Chemistry and Biotechnology
2008 Volume.51 No. 2 p.129 ~ p.135
The Role of ROS and p38 MAP kinase in Berberine-Induced Apoptosis on Human Hepatoma HepG2 Cells
Hyun Mee-Sun

Woo Won-Hong
Hur Jung-Mu
Kim Dong-Ho
Mun Yeun-Ja
Abstract
Berberine is an isoquinoline alkaloid used in traditional Chinese medicine and has been isolated from a variety of plants, such as Coptis chinensis and Phellodendron amurense. It has a wide spectrum of clinical applications such as in anti-tumor, anti-microbial, and anti-inflammatory activities. However, it is still unknown that berberine related with reactive oxygen species (ROS)-mediated apoptosis pathway in human hepatoma HepG2 cells. In the present study, we are examined the molecular mechanism of ROS- and p38 MAP kinase-mediated apoptosis by berberine in HepG2 cells. Berberine increased cytotoxicity effects by time- and does-dependent manner. LD50 was detected 50 ¥ìM at 48h of exposure to berberine. Nuclei cleavage and apoptotic DNA fragmentation were observed in cells treated with 50 ¥ìM of berberine for 48h. Moreover, berberine induced the activating of caspase-3, p53, p38 and Bax expression, whereas the expression of anti-apoptotic signaling pathways, Bcl-2, was decreased. Additionally, berberine-treated cells had an increased level of generation of ROS and nitric oxide (NO). These results indicated that berberine induces apoptosis of HepG2 cells may be mediated oxidative injury acts as an early and upstream change, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, p38 and p53 activation, caspase-3 activation, and consequent leading to apoptosis.
KEYWORD
Apoptosis, Berberine, Hepatoma, p38 MAPK, ROS
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