2009
Stixová, Lenka; Procházková, Jirina; Soucek, Karel; Hofmanová, Jirina; Kozubík, Alois
5-Lipoxygenase inhibitors potentiate 1alpha,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway. Journal Article
In: Molecular and cellular biochemistry, vol. 330, no. 1-2, pp. 229–238, 2009, ISSN: 1573-4919 0300-8177, (Place: Netherlands).
Abstract | Links | BibTeX | Tags: Arachidonate 5-Lipoxygenase/*genetics, Benzoquinones/pharmacology, Cell Differentiation/*drug effects, HL-60 Cells, Humans, Indoles/pharmacology, Lipoxygenase Inhibitors/*pharmacology, Monocytes/*cytology, p38 Mitogen-Activated Protein Kinases/*metabolism, Vitamin D/*analogs & derivatives/pharmacology
@article{stixova_5-lipoxygenase_2009,
title = {5-Lipoxygenase inhibitors potentiate 1alpha,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway.},
author = {Lenka Stixová and Jirina Procházková and Karel Soucek and Jirina Hofmanová and Alois Kozubík},
doi = {10.1007/s11010-009-0138-x},
issn = {1573-4919 0300-8177},
year = {2009},
date = {2009-10-01},
journal = {Molecular and cellular biochemistry},
volume = {330},
number = {1-2},
pages = {229–238},
abstract = {The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D(3) (VD3) induces differentiation toward the monocytic/macrophage lineage, demonstrated by the increased expression of CD11b and CD14, and the production of opsonized zymosan particles (OZP)-stimulated reactive oxygen species (ROS). Moreover, in more sensitive HL-60 cells, increased expression of 5-lipoxygenase (5-LPO), Mcl-1, IkappaB, and c-Jun, accompanied by the activation of p38 MAPK, was detected. These VD3 effects on HL-60 cell differentiation were significantly potentiated by 5-LPO inhibitors MK-886 and AA-861 and were inverted by SB202190 (SB), a p38 MAPK inhibitor. The inhibition of differentiation by SB was demonstrated by a reduction of CD14 expression and by a decrease in OZP-activated ROS production. These results indicated that p38 MAPK pathway is involved in 5-LPO inhibitors-dependent potentiation of VD3-induced monocytic differentiation.},
note = {Place: Netherlands},
keywords = {Arachidonate 5-Lipoxygenase/*genetics, Benzoquinones/pharmacology, Cell Differentiation/*drug effects, HL-60 Cells, Humans, Indoles/pharmacology, Lipoxygenase Inhibitors/*pharmacology, Monocytes/*cytology, p38 Mitogen-Activated Protein Kinases/*metabolism, Vitamin D/*analogs & derivatives/pharmacology},
pubstate = {published},
tppubtype = {article}
}
The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D(3) (VD3) induces differentiation toward the monocytic/macrophage lineage, demonstrated by the increased expression of CD11b and CD14, and the production of opsonized zymosan particles (OZP)-stimulated reactive oxygen species (ROS). Moreover, in more sensitive HL-60 cells, increased expression of 5-lipoxygenase (5-LPO), Mcl-1, IkappaB, and c-Jun, accompanied by the activation of p38 MAPK, was detected. These VD3 effects on HL-60 cell differentiation were significantly potentiated by 5-LPO inhibitors MK-886 and AA-861 and were inverted by SB202190 (SB), a p38 MAPK inhibitor. The inhibition of differentiation by SB was demonstrated by a reduction of CD14 expression and by a decrease in OZP-activated ROS production. These results indicated that p38 MAPK pathway is involved in 5-LPO inhibitors-dependent potentiation of VD3-induced monocytic differentiation.
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.
2003
Bryja, Vítezslav; Sedlácek, Jirí; Zahradnícková, Eva; Sevcíková, Sabina; Pacherník, Jirí; Soucek, Karel; Hofmanová, Jirina; Kozubík, Alois; Smarda, Jan
Lipoxygenase inhibitors enhance tumor suppressive effects of jun proteins on v-myb-transformed monoblasts BM2. Journal Article
In: Prostaglandins & other lipid mediators, vol. 72, no. 3-4, pp. 131–145, 2003, ISSN: 1098-8823, (Place: United States).
Abstract | Links | BibTeX | Tags: *Genes, 11, 14-Eicosatetraynoic Acid/metabolism, 5, 8, Animals, Antioxidants/pharmacology, Apoptosis, Arachidonic Acids/metabolism, Cell Cycle/drug effects, Cell Division/*drug effects, Cells, Chickens, Cultured, Humans, Lipoxygenase Inhibitors/*pharmacology, Lipoxygenase/*metabolism, Masoprocol/pharmacology, Monocytes/cytology/*drug effects/physiology, myb, Proto-Oncogene Proteins c-jun/genetics/*metabolism, Umbelliferones/pharmacology
@article{bryja_lipoxygenase_2003,
title = {Lipoxygenase inhibitors enhance tumor suppressive effects of jun proteins on v-myb-transformed monoblasts BM2.},
author = {Vítezslav Bryja and Jirí Sedlácek and Eva Zahradnícková and Sabina Sevcíková and Jirí Pacherník and Karel Soucek and Jirina Hofmanová and Alois Kozubík and Jan Smarda},
doi = {10.1016/s1098-8823(03)00052-2},
issn = {1098-8823},
year = {2003},
date = {2003-11-01},
journal = {Prostaglandins & other lipid mediators},
volume = {72},
number = {3-4},
pages = {131–145},
abstract = {Inhibitors of arachidonic acid (AA) conversion were described as suppressors of proliferation and inducers of differentiation of various leukemic cells. Certain AA metabolites have been shown to cooperate with Jun proteins that are important factors controlling cell proliferation, differentiation and apoptosis. Using lipoxygenase (LOX) inhibitors of various specifity we studied possible participation of lipoxygenase pathway in regulation of proliferation and apoptosis of v-myb-transformed chicken monoblasts BM2 and its functional interaction with Jun proteins. We found that nordihydroguaiaretic acid (NDGA) and esculetin (Esc) negatively regulate proliferation of BM2 cells causing accumulation in either G0/G1-phase (nordihydroguaiaretic acid) or S-phase (esculetin) of the cell cycle. BM2 cells can be also induced to undergo growth arrest and partial differentiation by ectopic expression of Jun proteins. We demonstrated that lipoxygenase inhibitors further enforce tumor suppressive capabilities of Jun proteins by inducing either more efficient cell cycle block and/or apoptosis in BM2 cells. This suggests that there is a cross-talk between the lipoxygenase- and Jun-directed pathways in regulation of differentiation and proliferation of monoblastic cells. Thus pharmacologic agents that specifically block lipoxygenase-catalyzed activity and enforce the effects of differentiation-inducers may be important components in anti-tumor therapies.},
note = {Place: United States},
keywords = {*Genes, 11, 14-Eicosatetraynoic Acid/metabolism, 5, 8, Animals, Antioxidants/pharmacology, Apoptosis, Arachidonic Acids/metabolism, Cell Cycle/drug effects, Cell Division/*drug effects, Cells, Chickens, Cultured, Humans, Lipoxygenase Inhibitors/*pharmacology, Lipoxygenase/*metabolism, Masoprocol/pharmacology, Monocytes/cytology/*drug effects/physiology, myb, Proto-Oncogene Proteins c-jun/genetics/*metabolism, Umbelliferones/pharmacology},
pubstate = {published},
tppubtype = {article}
}
Inhibitors of arachidonic acid (AA) conversion were described as suppressors of proliferation and inducers of differentiation of various leukemic cells. Certain AA metabolites have been shown to cooperate with Jun proteins that are important factors controlling cell proliferation, differentiation and apoptosis. Using lipoxygenase (LOX) inhibitors of various specifity we studied possible participation of lipoxygenase pathway in regulation of proliferation and apoptosis of v-myb-transformed chicken monoblasts BM2 and its functional interaction with Jun proteins. We found that nordihydroguaiaretic acid (NDGA) and esculetin (Esc) negatively regulate proliferation of BM2 cells causing accumulation in either G0/G1-phase (nordihydroguaiaretic acid) or S-phase (esculetin) of the cell cycle. BM2 cells can be also induced to undergo growth arrest and partial differentiation by ectopic expression of Jun proteins. We demonstrated that lipoxygenase inhibitors further enforce tumor suppressive capabilities of Jun proteins by inducing either more efficient cell cycle block and/or apoptosis in BM2 cells. This suggests that there is a cross-talk between the lipoxygenase- and Jun-directed pathways in regulation of differentiation and proliferation of monoblastic cells. Thus pharmacologic agents that specifically block lipoxygenase-catalyzed activity and enforce the effects of differentiation-inducers may be important components in anti-tumor therapies.