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Archives of Toxicology

, Volume 81, Issue 10, pp 719–728 | Cite as

Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL

  • Wen-Hsiu Hsu
  • Yih-Shou Hsieh
  • Hsing-Chun Kuo
  • Chun-Yuh Teng
  • Hai-I Huang
  • Chau-Jong Wang
  • Shun-Fa Yang
  • Yi-Sheng Liou
  • Wu-Hsien Kuo
Molecular Toxicology

Abstract

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.

Keywords

Berberine Colonic carcinoma ROS JNK p38 MAPK 

Notes

Acknowledgment

This study was supported by the Armed-Force Taichung General Hospital (grant number 0930001807) Republic of China.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Wen-Hsiu Hsu
    • 1
  • Yih-Shou Hsieh
    • 2
  • Hsing-Chun Kuo
    • 2
    • 4
  • Chun-Yuh Teng
    • 1
  • Hai-I Huang
    • 3
  • Chau-Jong Wang
    • 2
  • Shun-Fa Yang
    • 2
  • Yi-Sheng Liou
    • 5
    • 6
  • Wu-Hsien Kuo
    • 1
    • 2
    • 3
  1. 1.Division of Gastroenterology, Department of Internal MedicineArmed-Forces Taichung General HospitalTaiping City, TaichungTaiwan
  2. 2.Institute of Biochemistry and Biotechnology, School of MedicineChung Shan Medical UniversityTaichungTaiwan
  3. 3.Department of Medical TechnologyCentral Taiwan University of Science and TechnologyTaichungTaiwan
  4. 4.Department of Medical Research, Chang Gung Memorial HospitalKaohsiung Medical CenterKaohsiungTaiwan
  5. 5.Department of Public HealthNational Defense Medical CenterTaipeiTaiwan
  6. 6.Department of MedicineArmed-Forces Taichung General HospitalTaiping City, TaichungTaiwan

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