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

Jung Lim Kim, Seong Hye Park, Soyeon Jeong, Bo Ram Kim, Yoo Jin Na, Min Jee Jo, Yoon A. Jeong, Hye Kyeong Yun, Dae Yeong Kim, Bu Gyeom Kim, Sang Guan You, Sang Cheul Oh, Dae Hee Lee

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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.

Original languageEnglish
JournalNutrients
Volume11
Issue number5
DOIs
Publication statusPublished - 2019 May 11

Keywords

  • c-Jun N-terminal kinase (JNK)
  • endoplasmic reticulum (ER) stress
  • sea cucumber (SC)
  • X-linked inhibitor of apoptosis protein (XIAP)

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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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. G., Oh, S. C., & Lee, D. H. (2019). Sea Cucumber (Stichopus japonicas) F2 Enhanced TRAIL-Induced Apoptosis via XIAP Ubiquitination and ER Stress in Colorectal Cancer Cells. Nutrients, 11(5). https://doi.org/10.3390/nu11051061