Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells
- Authors
- Kim, Jung Lim; Park, Seong Hye; Jeong, So yeon; Kim, Bo Ram; Na, Yoo Jin; Jo, Min Jee; Jeong, Yoon A.; Yun, Hye Kyeong; Kim, Dae Yeong; Kim, Bu Gyeom; You, SangGuan; Oh, Sang Cheul; Lee, Dae Hee
- Issue Date
- May-2019
- Publisher
- MDPI
- Keywords
- sea cucumber (SC); endoplasmic reticulum (ER) stress; X-linked inhibitor of apoptosis protein (XIAP); c-Jun N-terminal kinase (JNK)
- Citation
- NUTRIENTS, v.11, no.5
- Indexed
- SCIE
SCOPUS
- Journal Title
- NUTRIENTS
- Volume
- 11
- Number
- 5
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2120
- DOI
- 10.3390/nu11051061
- ISSN
- 2072-6643
- Abstract
- Natural products have shown great promise in sensitizing cells to TNF-related apoptosis-inducing ligand (TRAIL) therapy. Sea cucumber (SC) extracts possess antitumor activity, and hence their potential to sensitize colorectal cancer (CRC) cells to TRAIL therapy was evaluated. This study used Western blotting to evaluate the combination effects of SC and TRAIL in CRC, and determined the molecular mechanism underlying these effects. SC fractions and TRAIL alone did not affect apoptosis; however, combined treatment dramatically induced the apoptosis of CRC cells, but not of normal colon cells. Combined treatment induced the expression of apoptotic proteins (poly (ADP-ribose) polymerase (PARP), caspase 3, and 8), and this effect was markedly inhibited by the ubiquitination of X-linked inhibitor of apoptosis protein (XIAP). SC did not affect the mRNA levels, but it increased proteasomal degradation and ubiquitination of the XIAP protein. Furthermore, SC induced reactive oxygen species (ROS) production, thereby activating c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress-related apoptotic pathways in CRC. Altogether, our results demonstrate that the SC F2 fraction may sensitize CRC cells to TRAIL-induced apoptosis through XIAP ubiquitination and ER stress.
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- Appears in
Collections - 3. Graduate School > Graduate School > 1. Journal Articles
- 2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
- 4. Research institute > Institute of Convergence New Drug Development > 1. Journal Articles
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