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

  • Molecular Toxicology
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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.

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Acknowledgment

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

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  1. Hsing-Chun Kuo

    Present address: Department of Medical Research, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, 833, Taiwan

Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, Armed-Forces Taichung General Hospital, No. 348, Section 2, Chung Shan Road, Taiping City, Taichung, Taiwan

    Wen-Hsiu Hsu, Chun-Yuh Teng & Wu-Hsien Kuo

  2. Institute of Biochemistry and Biotechnology, School of Medicine, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan

    Yih-Shou Hsieh, Hsing-Chun Kuo, Chau-Jong Wang, Shun-Fa Yang & Wu-Hsien Kuo

  3. Department of Medical Technology, Central Taiwan University of Science and Technology, No. 11 Pu-tzu Lane, Pu-tzu Road, Taichung, 406, Taiwan

    Hai-I Huang & Wu-Hsien Kuo

  4. Department of Public Health, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan

    Yi-Sheng Liou

  5. Department of Medicine, Armed-Forces Taichung General Hospital, Taiping City, Taichung, Taiwan

    Yi-Sheng Liou

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Hsu, WH., Hsieh, YS., Kuo, HC. et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch Toxicol 81, 719–728 (2007). https://doi.org/10.1007/s00204-006-0169-y

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