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Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells

  • Molecular Toxicology
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Abstract

Berberine, a main component of Coptidis Rhizoma, is a plant alkaloid with a long history of medicinal use in Chinese medicine. Berberine has indicated significant antimicrobial activity against a variety of organisms including bacteria, viruses, fungi. The mechanism by which berberine initiates apoptosis remains poorly understood. In the present study, we demonstrated that berberine exhibited significant cytotoxicity in hepatoma HepG2 cells but is ineffective in Chang liver cells. Herein we investigated cytotoxicity mechanism of berberine in HepG2 cells. The results showed that HepG2 cells underwent internucleosomal DNA fragmentation after 24-h treatment with berberine (50 μM). Moreover, berberine induced the activation of caspase-8 and −3, and caused the cleavage of poly ADP-ribose polymerase (PARP) and the cytochrome c release, whereas the expression of Bid and anti-apoptosis factor Bcl-XL were decreased markedly. The loss of mitochondrial membrane potential (Δ ψm) at 24 h and activation of Fas at 12 h were also seen in the berberine-treated HepG2 cells. These findings supported the fact that the inhibitors of caspases, DEVD-FMK, IETD-FMK and VAD-FMK, prevented apoptosis and restored the expression of Bcl-XL, Bcl-2 and Bid. These results indicated that the potential of anti-hepatoma activity of berberine may be mediated through a caspases-mitochondria-dependent pathway.

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Acknowledgements

The experiments comply with the current laws of Taiwan. This work was supported by the Chung Shan Medical University Research Fund and Liver Disease Prevention & Treatment Research Foundation Grant.

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Authors and Affiliations

  1. School of Applied Chemistry, Care and Management College, Chung Shan Medical University, No.110, Section 1, Chien-Kuo N. Road, Taichung, 402, Taiwan

    J. -M. Hwang, T. -H. Tseng & C. -Y. Chu

  2. Institute of Biochemistry and Biotechnology, Medical College, Chung Shan Medical University, No.110, Section 1, Chien-Kuo N. Road, Taichung, 402, Taiwan

    H. -C. Kuo & J. -Y. Liu

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  1. J. -M. Hwang
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  2. H. -C. Kuo
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  3. T. -H. Tseng
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  4. J. -Y. Liu
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  5. C. -Y. Chu
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Correspondence to C. -Y. Chu.

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Hwang, J.M., Kuo, H.C., Tseng, T.H. et al. Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells. Arch Toxicol 80, 62–73 (2006). https://doi.org/10.1007/s00204-005-0014-8

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  • DOI: https://doi.org/10.1007/s00204-005-0014-8

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