Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL
- 692 Downloads
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 μM 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.
KeywordsBerberine Colonic carcinoma ROS JNK p38 MAPK
This study was supported by the Armed-Force Taichung General Hospital (grant number 0930001807) Republic of China.
- Agarwal C, Sharma Y, Zhao J, Agarwal R (2000) A polyphenolic fraction from grape seeds causes irreversible growth inhibition of breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases activation and inducing G1 arrest and differentiation. Clin Cancer Res 6:2921–2930PubMedGoogle Scholar
- Assefa Z, Vantieghem A, Garmyn M, Declercq W, Vandenabeele P, Vandenheede JR, Bouillon R, Merlevede W, Agostinis P (2000) p38 mitogen-activated protein kinase regulates a novel, caspase-independent pathway for the mitochondrial cytochrome c release in ultraviolet B radiation-induced apoptosis. J Biol Chem 275:21416–21421PubMedCrossRefGoogle Scholar
- Richer C, Cogvadze V, Laffranchi R, Schlapbach R, Schweizer M, Suter M (1995) Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta 127:67–74Google Scholar
- Saeki K, Kobayashi N, Inazawa Y, Zhang H, Nishitoh H, Ichijo H, Isemura M, Yuo A (2002) Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and receptor-mediated apoptosis. Biochem J 368:705–720PubMedCrossRefGoogle Scholar