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Calyculin A causes sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by ROS-mediated down-regulation of cellular FLICE-inhibiting protein (c-FLIP) and by enhancing death receptor 4 mRNA stabilization

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Author(s)
Seon Min WooKyoung-jin MinTaeg Kyu Kwon
Publication Year
2012
Abstract
Calyculin A (Cal A) is a serine/threonine
phosphatase inhibitor that is capable of inducing apoptosis
in cancer cells. In this study, we examined whether Cal A
could modulate TRAIL-induced apoptosis in human renal
carcinoma-derived Caki cells. Our results show that Cal A
is capable of sensitizing Caki cells to TRAIL-induced
apoptosis, as well as U2OS human osteosarcoma cells and
A549 human lung adenocarcinoma epithelial cells. Cal A
increases intracellular ROS production and down-regulates
c-FLIP(L) expression. Interestingly, the down-regulation of
protein phosphatase 1 (PP1) by PP1 siRNA also reduced
c-FLIP(L) expression via reactive oxygen species production.
Furthermore, Cal A induced death receptor 4 (DR4)
mRNA and protein expression by enhancing DR4 mRNA
stability. We also found that PP4 siRNA up-regulated DR4
mRNA and protein expression. Collectively, our results
suggest that Cal A could enhance TRAIL-mediated apoptosis
via the down-regulation of c-FLIP(L) and the
up-regulation of DR4 in human renal cell carcinoma cell
line Caki.
Keywords Calyculin A TRAIL Death receptor
c-FLIP(L) Reactive oxygen species Protein phosphatase
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Apoptosis, Vol.17(11) : 1223-1234, 2012
Type
Article
ISSN
1360-8185
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35070
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