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Cited 18 time in webofscience Cited 22 time in scopus
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Cyclopamine sensitizes TRAIL-resistant gastric cancer cells to TRAIL-induced apoptosis via endoplasmic reticulum stress-mediated increase of death receptor 5 and survivin degradation

Authors
Na, Yoo JinLee, Dae-HeeKim, Jung LimKim, Bo RamPark, Seong HyeJo, Min JeeJeong, SoyeonKim, Hong JunLee, Suk-YoungJeong, Yoon A.Oh, Sang Cheul
Issue Date
Aug-2017
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Keywords
TRAIL-resistance; Cyclopamine; CHOP; Survivin; Death receptor 5
Citation
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v.89, pp 147 - 156
Pages
10
Indexed
SCI
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume
89
Start Page
147
End Page
156
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4779
DOI
10.1016/j.biocel.2017.06.010
ISSN
1357-2725
1878-5875
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is one of the most effective cancer treatments owing to its ability to selectively kill cancer cells, without affecting normal cells. However, it has been reported that several gastric cancer cells show resistance to TRAIL because of a scarcity of death receptor 5 (DR5) expressed on the cell surface. In this study, we show that cyclopamine sensitizes gastric cancer cells to TRAIL induced apoptosis by elevating the expression of DR5. Interestingly, survivin hampers the existence of DR5 protein under normal conditions and cyclopamine decreases the expression of survivin, thus acting as a TRAIL sensitizer. Mechanistically, cyclopamine induces endoplasmic reticulum (ER) stress via reactive oxygen species (ROS) and CHOP, the last protein of the ER stress pathway and it regulates the proteasome degradation of survivin. Taken together, our results indicate that cyclopamine can be used for combination therapy in TRAIL resistant gastric cancer cells.
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2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
4. Research institute > Institute of Convergence New Drug Development > 1. Journal Articles
3. Graduate School > Graduate School > 1. Journal Articles

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