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 Jin; Lee, Dae-Hee; Kim, Jung Lim; Kim, Bo Ram; Park, Seong Hye; Jo, Min Jee; Jeong, Soyeon; Kim, Hong Jun; Lee, Suk-Young; Jeong, 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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- Appears in
Collections - 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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