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.
2002
Pacherník, Jirí; Hampl, Ales; Soucek, Karel; Kovaríková, Martina; Andrysík, Zdenek; Hofmanová, Jirina; Kozubík, Alois
Multiple biological effects of inhibitors of arachidonic acid metabolism on human keratinocytes. Journal Article
In: Archives of dermatological research, vol. 293, no. 12, pp. 626–633, 2002, ISSN: 0340-3696, (Place: Germany).
Abstract | Links | BibTeX | Tags: 11, 14-Eicosatetraynoic Acid/pharmacology, 5, 8, Arachidonic Acid/*antagonists & inhibitors, Cell Differentiation/drug effects, Cell Division/drug effects, Cell Line, Cell Survival/drug effects, Cyclooxygenase Inhibitors/pharmacology, Humans, Indoles/pharmacology, Keratinocytes/cytology/*drug effects/*physiology, Lipoxygenase Inhibitors/pharmacology, Transformed, Umbelliferones/pharmacology
@article{pachernik_multiple_2002,
title = {Multiple biological effects of inhibitors of arachidonic acid metabolism on human keratinocytes.},
author = {Jirí Pacherník and Ales Hampl and Karel Soucek and Martina Kovaríková and Zdenek Andrysík and Jirina Hofmanová and Alois Kozubík},
doi = {10.1007/s00403-001-0288-5},
issn = {0340-3696},
year = {2002},
date = {2002-02-01},
journal = {Archives of dermatological research},
volume = {293},
number = {12},
pages = {626–633},
abstract = {BACKGROUND: Various compounds that inhibit processing of arachidonic acid (AA) are being intensively tested for their antitumour activity. However, the mechanisms responsible for such activity remain rather elusive. To approach this issue, we examined the effects of several structurally different inhibitors of AA metabolism in the human keratinocyte HaCaT cell line. METHODS: Several parameters were determined in HaCaT cells exposed to increasing concentrations of the inhibitors for 24 and/or 48 h. These included (1) oxidoreductase activity, total protein mass and cell cycle distribution to assess cell proliferation, (2) degradation of PARP protein to assess apoptosis, and (3) cell morphology, distribution of F-actin and expression of cytokeratins and E-cadherin to evaluate changes in differentiation status. RESULTS: While eicosatetraynoic acid (ETYA), nordihydroguaiaretic acid (NDGA), esculetin and MK-886 reduced proliferation of HaCaT cells, the cyclooxygenase inhibitors indomethacin and piroxicam had no such effects. Esculetin and NDGA arrested cells in S phase, and ETYA and MK-886 delayed cell progression through G(1) phase. Higher concentrations of NDGA, MK886 and/or ETYA caused cleavage of PARP. No changes in the expression of cytokeratins and E-cadherin were observed upon treatment with any of the inhibitors. However, esculetin induced redistribution of F-actin accompanied by increased cell adhesion and size. CONCLUSION: Our findings indicate that, in addition to their ability to inhibit cell proliferation and to induce apoptosis, lipoxygenase inhibitors and/or ETYA may also elicit other important physiological responses in HaCaT keratinocytes.},
note = {Place: Germany},
keywords = {11, 14-Eicosatetraynoic Acid/pharmacology, 5, 8, Arachidonic Acid/*antagonists & inhibitors, Cell Differentiation/drug effects, Cell Division/drug effects, Cell Line, Cell Survival/drug effects, Cyclooxygenase Inhibitors/pharmacology, Humans, Indoles/pharmacology, Keratinocytes/cytology/*drug effects/*physiology, Lipoxygenase Inhibitors/pharmacology, Transformed, Umbelliferones/pharmacology},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Various compounds that inhibit processing of arachidonic acid (AA) are being intensively tested for their antitumour activity. However, the mechanisms responsible for such activity remain rather elusive. To approach this issue, we examined the effects of several structurally different inhibitors of AA metabolism in the human keratinocyte HaCaT cell line. METHODS: Several parameters were determined in HaCaT cells exposed to increasing concentrations of the inhibitors for 24 and/or 48 h. These included (1) oxidoreductase activity, total protein mass and cell cycle distribution to assess cell proliferation, (2) degradation of PARP protein to assess apoptosis, and (3) cell morphology, distribution of F-actin and expression of cytokeratins and E-cadherin to evaluate changes in differentiation status. RESULTS: While eicosatetraynoic acid (ETYA), nordihydroguaiaretic acid (NDGA), esculetin and MK-886 reduced proliferation of HaCaT cells, the cyclooxygenase inhibitors indomethacin and piroxicam had no such effects. Esculetin and NDGA arrested cells in S phase, and ETYA and MK-886 delayed cell progression through G(1) phase. Higher concentrations of NDGA, MK886 and/or ETYA caused cleavage of PARP. No changes in the expression of cytokeratins and E-cadherin were observed upon treatment with any of the inhibitors. However, esculetin induced redistribution of F-actin accompanied by increased cell adhesion and size. CONCLUSION: Our findings indicate that, in addition to their ability to inhibit cell proliferation and to induce apoptosis, lipoxygenase inhibitors and/or ETYA may also elicit other important physiological responses in HaCaT keratinocytes.