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Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells

1
Department of Oncology, Korea University Guro Hospital, Seoul 152-703, Korea
2
Graduate School of Medicine, Korea University College of Medicine, Seoul 152-703, Korea
3
Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangwon 210-702, Korea
*
Authors to whom correspondence should be addressed.
These aurthors contributed equally to this study.
Nutrients 2019, 11(5), 1061; https://doi.org/10.3390/nu11051061
Received: 2 May 2019 / Accepted: 8 May 2019 / Published: 11 May 2019
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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. View Full-Text
Keywords: sea cucumber (SC); endoplasmic reticulum (ER) stress; X-linked inhibitor of apoptosis protein (XIAP); c-Jun N-terminal kinase (JNK) sea cucumber (SC); endoplasmic reticulum (ER) stress; X-linked inhibitor of apoptosis protein (XIAP); c-Jun N-terminal kinase (JNK)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kim, J.L.; Park, S.H.; Jeong, S.; Kim, B.R.; Na, Y.J.; Jo, M.J.; Jeong, Y.A.; Yun, H.K.; Kim, D.Y.; Kim, B.G.; You, S.; Oh, S.C.; Lee, D.-H. Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells. Nutrients 2019, 11, 1061.

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