Codium fragile F2 sensitize colorectal cancer cells to TRAIL-induced apoptosis via c-FLIP ubiquitination

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

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11 Citations (Scopus)


This study demonstrates that combined treatment with subtoxic doses of Codium extracts (CE), a flavonoid found in many fruits and vegetables, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), induces apoptosis in TRAIL-resistant colorectal cancer (CRC) cells. Effective induction of apoptosis by combined treatment with CE and TRAIL was not blocked by Bcl-xL overexpression, which is known to confer resistance to various chemotherapeutic agents. While TRAIL-mediated proteolytic processing of procaspase-3 was partially blocked in various CRC cells treated with TRAIL alone, co-treatment with CE efficiently recovered TRAIL-induced caspase activation. We observed that CE treatment of CRC cells did not change the expression of anti-apoptotic proteins and pro-apoptotic proteins, including death receptors (DR4 and DR5). However, CE treatment markedly reduced the protein level of the short form of the cellular FLICE-inhibitory protein (c-FLIPS), an inhibitor of caspase-8, via proteasome-mediated degradation. Collectively, these observations show that CE recovers TRAIL sensitivity in various CRC cells via down-regulation of c-FLIPS.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBiochemical and biophysical research communications
Issue number1
Publication statusPublished - 2019 Jan 1

Bibliographical note

Funding Information:
This work was supported by grant from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) ( NRF-2017R1A2B2011684 , NRF-2015R1D1A1A01058303 ). This research was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [ 2018R1A6A1A03023584 ] to SG You.

Publisher Copyright:
© 2018


  • CHX
  • Codium extracts (CE)
  • Cycloheximide
  • FITC
  • FLICE-Like inhibitory protein
  • FLIP
  • Fluorescein isothiocyanate
  • PARP
  • PBS
  • PI
  • Phosphate-buffered saline
  • Poly (ADP-Ribose) polymerase
  • Propidium iodide
  • Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
  • TNF
  • TNF-Related apoptosis-inducing ligand
  • Tumor necrosis factor
  • Ubiquitination
  • c-FLIP

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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