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

Title
Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins
Author(s)
이태진이성준[이성준]성언기송인환김주영권택규[권택규]
Keywords
DR5 UP-REGULATION; DEATH RECEPTOR 5; LEUKEMIA-CELLS; CANCER-CELLS; OXIDATIVE STRESS; CELLULAR FLIP; TUMOR-CELLS; IN-VITRO; PATHWAY; DEGRADATION
Issue Date
201102
Publisher
SPANDIDOS PUBL LTD
Citation
INTERNATIONAL JOURNAL OF ONCOLOGY, v.38, no.2, pp.485 - 492
Abstract
Berberine (BBR) is an isoquinoline alkaloid which has a wide spectrum of clinical applications including antitumor, 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 MG 132 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 Mel-1 downregulation.
URI
http://hdl.handle.net/YU.REPOSITORY/25695http://dx.doi.org/10.3892/ijo.2010.878
ISSN
1019-6439
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의과대학 > 해부학교실 > Articles
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