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, Sanguan You, Sang Cheul Oh, Dae Hee Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Ubiquitination
Colorectal Neoplasms
Apoptosis Regulatory Proteins
Cells
Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein
Death Domain Receptors
Caspase 8
Vegetables
Corrosion inhibitors
Proteasome Endopeptidase Complex
Caspases
Fruits
Flavonoids
Caspase 3
Tumor Necrosis Factor-alpha
Chemical activation
Ligands
Degradation
Fruit

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Codium fragile F2 sensitize colorectal cancer cells to TRAIL-induced apoptosis via c-FLIP ubiquitination. / Park, Seong Hye; Kim, Jung Lim; Jeong, Soyeon; Kim, Bo Ram; Na, Yoo Jin; Jo, Min Jee; Yun, Hye Kyeong; Jeong, Yoon A.; Kim, Dae Yeong; Kim, Bu Gyeom; You, Sanguan; Oh, Sang Cheul; Lee, Dae Hee.

In: Biochemical and Biophysical Research Communications, 01.01.2018.

Research output: Contribution to journalArticle

Park, Seong Hye ; Kim, Jung Lim ; Jeong, Soyeon ; Kim, Bo Ram ; Na, Yoo Jin ; Jo, Min Jee ; Yun, Hye Kyeong ; Jeong, Yoon A. ; Kim, Dae Yeong ; Kim, Bu Gyeom ; You, Sanguan ; Oh, Sang Cheul ; Lee, Dae Hee. / Codium fragile F2 sensitize colorectal cancer cells to TRAIL-induced apoptosis via c-FLIP ubiquitination. In: Biochemical and Biophysical Research Communications. 2018.
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abstract = "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.",
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AU - Kim, Jung Lim

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AU - Kim, Bo Ram

AU - Na, Yoo Jin

AU - Jo, Min Jee

AU - Yun, Hye Kyeong

AU - Jeong, Yoon A.

AU - Kim, Dae Yeong

AU - Kim, Bu Gyeom

AU - You, Sanguan

AU - Oh, Sang Cheul

AU - Lee, Dae Hee

PY - 2018/1/1

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N2 - 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.

AB - 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.

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