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 language | English |
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Pages (from-to) | 1-8 |
Number of pages | 8 |
Journal | Biochemical and biophysical research communications |
Volume | 508 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2019 Jan 1 |
Keywords
- 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
- SDS-PAGE
- Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- TNF
- TNF-Related apoptosis-inducing ligand
- TRAIL
- TRAIL
- Tumor necrosis factor
- Ubiquitination
- c-FLIP
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology