Berberine is the major constituent of Coptidis Rhizoma with multiple pharmacological activities, including anti-
inflammation, promotion of apoptosis and anticancer potential effect.
Mitogen-activated protein kinase (MAPK) and
reactive oxygen species (ROS) may contribute to the causal relationship between
tumorigenesis and pro-apoptotic function.
Berberine is studied for the mechanism of its action in apoptotic pathway in human colonic
carcinoma cell. Treatment of SW620 cells with 50 microM
berberine resulted in activation of the
caspase 3 and
caspase 8, cleavage of
poly ADP-ribose polymerase (PARP) and the release of
cytochrome c; whereas, the expression of BID and anti-apoptosis factor c-IAP1, Bcl-2, and Bcl-(XL) were decreased markedly.
Berberine-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of JNK and
p38 MAPK, as well as generation of the ROS. Furthermore, the induction of apoptosis was alleviated by inhibitors specific for JNK and p38. In addition, there was an increase in the cellular levels of phospho-c-Jun, FasL and t-BID in the
berberine-induced apoptosis via the activation of JNK and p38 signaling modules. NAC administration, a scavenger of ROS, reversed
berberine-induced apoptosis effects via inhibition of JNK, p38 and c-jun activation, and FasL and t-BID expression. These results leads us to speculate that
berberine may play an apoptotic cascade in SW620 cells by activation of the JNK/p38 pathway and induction of ROS production, providing a new mechanism for
berberine-induced cell death in human
colon cancer cells.