2006
Stika, Jirí; Vondrácek, Jan; Hofmanová, Jirina; Simek, Vladimír; Kozubík, Alois
MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis. Journal Article
In: Cancer letters, vol. 237, no. 2, pp. 263–271, 2006, ISSN: 0304-3835, (Place: Ireland).
Abstract | Links | BibTeX | Tags: *Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism
@article{stika_mk-886_2006,
title = {MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.},
author = {Jirí Stika and Jan Vondrácek and Jirina Hofmanová and Vladimír Simek and Alois Kozubík},
doi = {10.1016/j.canlet.2005.06.012},
issn = {0304-3835},
year = {2006},
date = {2006-06-01},
journal = {Cancer letters},
volume = {237},
number = {2},
pages = {263–271},
abstract = {We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.},
note = {Place: Ireland},
keywords = {*Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism},
pubstate = {published},
tppubtype = {article}
}
We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.
2004
Kovaríková, Martina; Hofmanová, Jirina; Soucek, Karel; Kozubík, Alois
The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status. Journal Article
In: Differentiation; research in biological diversity, vol. 72, no. 1, pp. 23–31, 2004, ISSN: 0301-4681, (Place: England).
Abstract | Links | BibTeX | Tags: *Flavanones, Adenocarcinoma/drug therapy/pathology, Arachidonate 5-Lipoxygenase/metabolism, Arachidonic Acid/*metabolism, Butyrates/pharmacology, Caspase 3, Caspases/drug effects/metabolism, Cell Cycle/drug effects, Cell Differentiation/*drug effects, Cell Division/drug effects, Colonic Neoplasms/drug therapy/metabolism/pathology, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors/*pharmacology, Drug Synergism, Flavonoids/pharmacology, HT29 Cells/drug effects, Humans, Indomethacin/pharmacology, Isoenzymes/antagonists & inhibitors/metabolism, Lipoxygenase Inhibitors/*pharmacology, Masoprocol/pharmacology, Membrane Proteins, Niflumic Acid/pharmacology, Prostaglandin-Endoperoxide Synthases/metabolism, Tumor Necrosis Factor-alpha/*pharmacology
@article{kovarikova_effects_2004,
title = {The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status.},
author = {Martina Kovaríková and Jirina Hofmanová and Karel Soucek and Alois Kozubík},
doi = {10.1111/j.1432-0436.2004.07201006.x},
issn = {0301-4681},
year = {2004},
date = {2004-02-01},
journal = {Differentiation; research in biological diversity},
volume = {72},
number = {1},
pages = {23–31},
abstract = {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.},
note = {Place: England},
keywords = {*Flavanones, Adenocarcinoma/drug therapy/pathology, Arachidonate 5-Lipoxygenase/metabolism, Arachidonic Acid/*metabolism, Butyrates/pharmacology, Caspase 3, Caspases/drug effects/metabolism, Cell Cycle/drug effects, Cell Differentiation/*drug effects, Cell Division/drug effects, Colonic Neoplasms/drug therapy/metabolism/pathology, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors/*pharmacology, Drug Synergism, Flavonoids/pharmacology, HT29 Cells/drug effects, Humans, Indomethacin/pharmacology, Isoenzymes/antagonists & inhibitors/metabolism, Lipoxygenase Inhibitors/*pharmacology, Masoprocol/pharmacology, Membrane Proteins, Niflumic Acid/pharmacology, Prostaglandin-Endoperoxide Synthases/metabolism, Tumor Necrosis Factor-alpha/*pharmacology},
pubstate = {published},
tppubtype = {article}
}
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.