2008
Ondrousková, Eva; Soucek, Karel; Horváth, Viktor; Smarda, Jan
Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis. Journal Article
In: Leukemia research, vol. 32, no. 4, pp. 599–609, 2008, ISSN: 0145-2126, (Place: England).
Abstract | Links | BibTeX | Tags: Animals, Antineoplastic Agents/*pharmacology, Apoptosis/*drug effects, Arsenic Trioxide, Arsenicals/pharmacology, Autophagy/*drug effects, Blotting, Camptothecin/pharmacology, Caspases/*metabolism, Cell Line, Cell Transformation, Chickens, Cycloheximide/pharmacology, Fluorescence, Genes, Humans, Microscopy, myb/physiology, Necrosis, Neoplastic/*pathology, Oxides/pharmacology, Signal Transduction/*drug effects, Transformed, U937 Cells/drug effects, Western
@article{ondrouskova_alternative_2008,
title = {Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis.},
author = {Eva Ondrousková and Karel Soucek and Viktor Horváth and Jan Smarda},
doi = {10.1016/j.leukres.2007.05.012},
issn = {0145-2126},
year = {2008},
date = {2008-04-01},
journal = {Leukemia research},
volume = {32},
number = {4},
pages = {599–609},
abstract = {Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.},
note = {Place: England},
keywords = {Animals, Antineoplastic Agents/*pharmacology, Apoptosis/*drug effects, Arsenic Trioxide, Arsenicals/pharmacology, Autophagy/*drug effects, Blotting, Camptothecin/pharmacology, Caspases/*metabolism, Cell Line, Cell Transformation, Chickens, Cycloheximide/pharmacology, Fluorescence, Genes, Humans, Microscopy, myb/physiology, Necrosis, Neoplastic/*pathology, Oxides/pharmacology, Signal Transduction/*drug effects, Transformed, U937 Cells/drug effects, Western},
pubstate = {published},
tppubtype = {article}
}
Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.
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.
Nemajerová, Alice; Smarda, Jan; Jurdic, Pierre; Kubala, Lukás; Soucek, Karel; Smardová, Jana
Trichostatin A suppresses transformation by the v-myb oncogene in BM2 cells. Journal Article
In: Journal of hematotherapy & stem cell research, vol. 12, no. 2, pp. 225–235, 2003, ISSN: 1525-8165, (Place: United States).
Abstract | Links | BibTeX | Tags: Acetylation, Animals, Cell Cycle, Cell Differentiation, Cell Line, Cell Transformation, Chickens, Chromatin Assembly and Disassembly/physiology, Genes, Histone Deacetylases/drug effects, Histones/metabolism/physiology, Hydroxamic Acids/*pharmacology, Macrophages/cytology, myb/drug effects/*physiology, Transformed, Viral/*drug effects
@article{nemajerova_trichostatin_2003,
title = {Trichostatin A suppresses transformation by the v-myb oncogene in BM2 cells.},
author = {Alice Nemajerová and Jan Smarda and Pierre Jurdic and Lukás Kubala and Karel Soucek and Jana Smardová},
doi = {10.1089/152581603321628368},
issn = {1525-8165},
year = {2003},
date = {2003-04-01},
journal = {Journal of hematotherapy & stem cell research},
volume = {12},
number = {2},
pages = {225–235},
abstract = {BM2 cells are chicken monoblasts transformed by the v-myb oncogene of avian myeloblastosis virus. The constitutively high v-myb expression interferes with the terminal differentiation of BM2 cells, but these cells can be induced to differentiate into macrophage-like cells by phorbol esters. Histone acetylation plays an important role in regulation of transcription and is particularly relevant to the regulation and pathology of hematopoiesis. In the present study, we examined the contribution of elevated histone acetylation to the differentiation of BM2 cells. Inhibition of the activity of endogenous histone deacetylases by trichostatin A (TSA) resulted in histone hyperacetylation causing cell cycle arrest and differentiation of BM2 cells into macrophage polykaryons. TSA did not affect the level of v-Myb protein in BM2 cells, but it downregulated its transcription activation capability. This suggests that chromatin remodeling can be significantly engaged in regulation of proliferation and differentiation of leukemic cells.},
note = {Place: United States},
keywords = {Acetylation, Animals, Cell Cycle, Cell Differentiation, Cell Line, Cell Transformation, Chickens, Chromatin Assembly and Disassembly/physiology, Genes, Histone Deacetylases/drug effects, Histones/metabolism/physiology, Hydroxamic Acids/*pharmacology, Macrophages/cytology, myb/drug effects/*physiology, Transformed, Viral/*drug effects},
pubstate = {published},
tppubtype = {article}
}
BM2 cells are chicken monoblasts transformed by the v-myb oncogene of avian myeloblastosis virus. The constitutively high v-myb expression interferes with the terminal differentiation of BM2 cells, but these cells can be induced to differentiate into macrophage-like cells by phorbol esters. Histone acetylation plays an important role in regulation of transcription and is particularly relevant to the regulation and pathology of hematopoiesis. In the present study, we examined the contribution of elevated histone acetylation to the differentiation of BM2 cells. Inhibition of the activity of endogenous histone deacetylases by trichostatin A (TSA) resulted in histone hyperacetylation causing cell cycle arrest and differentiation of BM2 cells into macrophage polykaryons. TSA did not affect the level of v-Myb protein in BM2 cells, but it downregulated its transcription activation capability. This suggests that chromatin remodeling can be significantly engaged in regulation of proliferation and differentiation of leukemic cells.