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

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Author(s)
SUNG-JUN LEEHYO-JEONG NOHEON-GI SUNGIN-HWAN SONGJOO-YOUNG KIMTAEG KYU KWONTAE-JIN LEE
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
International Journal of Oncology
Issued Date
2011
Volume
38
Issue
2
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 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 TRAILinduced
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 downregulation.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
SUNG-JUN LEE et al. (2011). Berberine sensitizes TRAIL-induced apoptosis
through proteasome-mediated downregulation
of c-FLIP and Mcl-1 proteins. International Journal of Oncology, 38(2), 485–492. doi: 10.3892/ijo.2010.878
Type
Article
ISSN
1019-6439
Source
http://www.spandidos-publications.com/ijo/38/2/485
DOI
10.3892/ijo.2010.878
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36001
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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