The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
15008823
DOI
10.1111/j.1432-0436.2004.07201006.x
PII: S0301-4681(09)60283-8
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma drug therapy pathology MeSH
- Arachidonate 5-Lipoxygenase metabolism MeSH
- Cell Differentiation drug effects MeSH
- Cell Division drug effects MeSH
- Cell Cycle drug effects MeSH
- HT29 Cells drug effects MeSH
- Butyrates pharmacology MeSH
- Cyclooxygenase 2 MeSH
- Prostaglandin-Endoperoxide Synthases metabolism MeSH
- Flavanones * MeSH
- Flavonoids pharmacology MeSH
- Indomethacin pharmacology MeSH
- Cyclooxygenase 2 Inhibitors MeSH
- Cyclooxygenase Inhibitors pharmacology MeSH
- Lipoxygenase Inhibitors pharmacology MeSH
- Isoenzymes antagonists & inhibitors metabolism MeSH
- Caspase 3 MeSH
- Caspases drug effects metabolism MeSH
- Arachidonic Acid metabolism MeSH
- Niflumic Acid pharmacology MeSH
- Masoprocol pharmacology MeSH
- Humans MeSH
- Membrane Proteins MeSH
- Colonic Neoplasms drug therapy metabolism pathology MeSH
- Drug Synergism MeSH
- Tumor Necrosis Factor-alpha pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Arachidonate 5-Lipoxygenase MeSH
- baicalein MeSH Browser
- Butyrates MeSH
- CASP3 protein, human MeSH Browser
- Cyclooxygenase 2 MeSH
- Prostaglandin-Endoperoxide Synthases MeSH
- Flavanones * MeSH
- Flavonoids MeSH
- Indomethacin MeSH
- Cyclooxygenase 2 Inhibitors MeSH
- Cyclooxygenase Inhibitors MeSH
- Lipoxygenase Inhibitors MeSH
- Isoenzymes MeSH
- Caspase 3 MeSH
- Caspases MeSH
- Arachidonic Acid MeSH
- Niflumic Acid MeSH
- Masoprocol MeSH
- Membrane Proteins MeSH
- PTGS2 protein, human MeSH Browser
- Tumor Necrosis Factor-alpha MeSH
The level of differentiation could influence sensitivity of colonic epithelial cells to various stimuli. In our study, the effects of TNF-alpha, inhibitors of arachidonic acid (AA) metabolism (baicalein, BA; indomethacin, INDO; niflumic acid, NA; nordihydroguaiaretic acid, NDGA), and/or their combinations on undifferentiated or sodium butyrate (NaBt)-differentiated human colon adenocarcinoma HT-29 cells were compared. NaBt-treated cells became growth arrested (blocked in G0/G1 phase of the cell cycle), and showed down-regulated Bcl-xL and up-regulated Bak proteins and increased expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). These cells were more perceptive to anti-proliferative and apoptotic effects of TNF-alpha. Both inhibitors of LOX (BA and NDGA) and COX (INDO and NA) in higher concentrations modulated cell cycle changes accompanying NaBt-induced differentiation and induced various level of cell death in undifferentiated and differentiated cells. Most important is our finding that TNF-alpha action on proliferation and cell death can be potentiated by co-treatment of cells with AA metabolism inhibitors, and that these effects were more significant in undifferentiated cells. TNF-alpha and INDO co-treatment was associated with accumulation of cells in G0/G1 cell cycle phase, increased reactive oxygen species production, and elevated caspase-3 activity. These results indicate the role of differentiation status in the sensitivity of HT-29 cells to the anti-proliferative and proapoptotic effects of TNF-alpha, AA metabolism inhibitors, and their combinations, and imply promising possibility for novel anti-cancer strategies.
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