Abstract
Suppression of resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates, was studied using small molecule inhibitors of the activation of the transcription factor NF-kB - NF-k9 Activation Inhibitor IV and JSH-23 at non-toxic concentrations. NF-kB Activation Inhibitor IV and JSH-23 reduced resistance in the acute myeloid leukemia cells in multicellular aggregates to cytotoxic action of recombinant protein izTRAIL. It is shown that the use of these inhibitors decreased the phosphorylation of the RelA (p65) as a main marker activation of the transcription factor NF-kB. We discuss a possible reason for increasing resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates.
MeSH terms
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Apoptosis / drug effects
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Cell Survival / drug effects
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Drug Resistance, Neoplasm / genetics
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Humans
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Leukemia, Myeloid, Acute / drug therapy*
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Leukemia, Myeloid, Acute / genetics
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NF-kappa B / antagonists & inhibitors*
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Phenylenediamines / administration & dosage
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Phosphorylation / drug effects
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Protein Aggregates / drug effects
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TNF-Related Apoptosis-Inducing Ligand / administration & dosage
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TNF-Related Apoptosis-Inducing Ligand / metabolism*
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Transcription Factor RelA / chemistry
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Transcription Factor RelA / metabolism*
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Transcriptional Activation / drug effects
Substances
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4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine
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NF-kappa B
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Phenylenediamines
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Protein Aggregates
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RELA protein, human
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Transcription Factor RelA