Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins

  • Authors:
    • Sung-Jun Lee
    • Hyo-Jeong Noh
    • Eon-Gi Sung
    • In-Hwan Song
    • Joo-Young Kim
    • Taeg Kyu Kwon
    • Tae-Jin Lee
  • View Affiliations

  • Published online on: December 17, 2010     https://doi.org/10.3892/ijo.2010.878
  • Pages: 485-492
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Abstract

Berberine (BBR) is an isoquinoline alkaloid which has a wide spectrum of clinical applications including anti-tumor, anti-microbial and anti-inflammatory activities. In this study, we showed that co-treatment with subtoxic doses of BBR and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human renal cancer cells, Caki cells, but not in normal tubular kidney cells. Treatment of Caki cells with BBR resulted in downregulation of c-FLIP and Mcl-1 proteins in a dose-dependent manner. The BBR-induced downregulation of c-FLIP and Mcl-1 proteins were involved in proteasome dependent pathways, which was confirmed by the result that pre-treatment with the proteasome inhibitor MG132 inhibited berberine-induced downregulation of the c-FLIP and Mcl-1 proteins. Pretreatment with N-acetyl-l-cysteine (NAC) significantly inhibited the cell death induced by the combined treatment with BBR and TRAIL as well as recovered the expression levels of c-FLIP and Mcl-1 downregulated by treatment with BBR. These results suggested that BBR-stimulated TRAIL-induced apoptosis is dependent on the generation of reactive oxygen species through the downregulation of c-FLIP and Mcl-1 proteins. In conclusion, this study demonstrates that BBR enhances TRAIL-induced apoptosis in human renal cancer cells by ROS-mediated c-FLIP and Mcl-1 down-regulation.

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February 2011
Volume 38 Issue 2

Print ISSN: 1019-6439
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Spandidos Publications style
Lee S, Noh H, Sung E, Song I, Kim J, Kwon TK and Lee T: Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins. Int J Oncol 38: 485-492, 2011.
APA
Lee, S., Noh, H., Sung, E., Song, I., Kim, J., Kwon, T.K., & Lee, T. (2011). Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins. International Journal of Oncology, 38, 485-492. https://doi.org/10.3892/ijo.2010.878
MLA
Lee, S., Noh, H., Sung, E., Song, I., Kim, J., Kwon, T. K., Lee, T."Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins". International Journal of Oncology 38.2 (2011): 485-492.
Chicago
Lee, S., Noh, H., Sung, E., Song, I., Kim, J., Kwon, T. K., Lee, T."Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins". International Journal of Oncology 38, no. 2 (2011): 485-492. https://doi.org/10.3892/ijo.2010.878