Different modulation of TRAIL-induced apoptosis by inhibition of pro-survival pathways in TRAIL-sensitive and TRAIL-resistant colon cancer cells
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17113582
DOI
10.1016/j.febslet.2006.11.004
PII: S0014-5793(06)01312-3
Knihovny.cz E-resources
- MeSH
- Enzyme Activation drug effects MeSH
- Apoptosis drug effects MeSH
- HT29 Cells MeSH
- Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors MeSH
- Phosphorylation drug effects MeSH
- Enzyme Inhibitors pharmacology MeSH
- Phosphoinositide-3 Kinase Inhibitors MeSH
- Caspase 8 metabolism MeSH
- Keratin-18 metabolism MeSH
- Glycogen Synthase Kinase 3 metabolism MeSH
- Glycogen Synthase Kinase 3 beta MeSH
- Humans MeSH
- Mitogen-Activated Protein Kinase 1 antagonists & inhibitors MeSH
- Mitogen-Activated Protein Kinase 3 antagonists & inhibitors MeSH
- Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors MeSH
- Neoplasm Proteins metabolism MeSH
- Colonic Neoplasms pathology MeSH
- Poly(ADP-ribose) Polymerases metabolism MeSH
- Myeloid Cell Leukemia Sequence 1 Protein MeSH
- TNF-Related Apoptosis-Inducing Ligand pharmacology MeSH
- Proto-Oncogene Proteins c-akt antagonists & inhibitors MeSH
- Proto-Oncogene Proteins c-bcl-2 metabolism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Extracellular Signal-Regulated MAP Kinases MeSH
- GSK3B protein, human MeSH Browser
- Enzyme Inhibitors MeSH
- Phosphoinositide-3 Kinase Inhibitors MeSH
- Caspase 8 MeSH
- Keratin-18 MeSH
- Glycogen Synthase Kinase 3 MeSH
- Glycogen Synthase Kinase 3 beta MeSH
- Mitogen-Activated Protein Kinase 1 MeSH
- Mitogen-Activated Protein Kinase 3 MeSH
- Mitogen-Activated Protein Kinase Kinases MeSH
- Neoplasm Proteins MeSH
- Poly(ADP-ribose) Polymerases MeSH
- Myeloid Cell Leukemia Sequence 1 Protein MeSH
- TNF-Related Apoptosis-Inducing Ligand MeSH
- Proto-Oncogene Proteins c-akt MeSH
- Proto-Oncogene Proteins c-bcl-2 MeSH
Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro-survival and apoptotic signals. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (HT-29) and TRAIL-resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL-induced apoptosis in HT-29 cells, but not in SW620 cells. We report a different regulation of the level of an anti-apoptotic Mcl-1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3beta.
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