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FTY720 enhances TRAIL-mediated apoptosis by up-regulating DR5 and down-regulating Mcl-1 in cancer cells

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Author(s)
Seon Min WooBo Ram SeoKyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Oncotarget
Issued Date
2015
Volume
6
Issue
13
Keyword
FTY720TRAILDR5Mcl-1apoptosis
Abstract
FTY720, Fingolimod, is a functional antagonist to the sphingosine-1-phoaphate
(S1P) receptor and an inhibitor of sphingosine kinase 1. Here, we showed that a
combination of FTY720 and TRAIL induced apoptosis in human renal, breast, and
colon carcinoma cells. Most importantly, this combination had no effect on normal
cells. Furthermore, the combined treatment with FTY720 and TRAIL reduced tumor
growth in xenograft models. FTY720 up-regulated death receptor (DR)5 at posttranslational
level. Knockdown of DR5 markedly blocked apoptosis induced by the
combined treatment. FTY720 also inhibited Mcl-1 expression at the post-translational
level. Over-expression of Mcl-1 blocked apoptosis induced by FTY720 and TRAIL.
Interestingly, phospho-FTY720 and inhibitors of sphingosine kinase failed to enhance
TRAIL-induced apoptosis. Thus, FTY720 enables TRAIL-induced apoptosis through
up-regulation of DR5 and down-regulation of Mcl-1 in human cancer cells.
Keywords: FTY720, TRAIL, DR5, Mcl-1, apoptosis
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Seon Min Woo et al. (2015). FTY720 enhances TRAIL-mediated apoptosis by up-regulating DR5 and down-regulating Mcl-1 in cancer cells. Oncotarget, 6(13), 11614–11626. doi: 10.18632/oncotarget.3426
Type
Article
ISSN
1949-2553
DOI
10.18632/oncotarget.3426
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33614
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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