TY - JOUR AB - 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. AD - Department of Anatomy, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong Nam-Gu, Daegu 705-717, Republic of Korea null AU - Lee,Sung-Jun AU - Noh,Hyo-Jeong AU - Sung,Eon-Gi AU - Song,In-Hwan AU - Kim,Joo-Young AU - Kwon,Taeg ,Kyu AU - Lee,Tae-Jin DA - 2011/02/01 DO - 10.3892/ijo.2010.878 EP - 492 IS - 2 JO - Int J Oncol KW - berberine TRAIL c-FLIP Mcl-1 ROS proteasome PY - 2011 SN - 1019-6439 1791-2423 SP - 485 ST - Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins T2 - International Journal of Oncology TI - Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins UR - https://doi.org/10.3892/ijo.2010.878 VL - 38 ER -