Abstract
Constitutive activation of NF-κB and STAT3 plays an important role in the cellular proliferation and survival of multiple myeloma cells. We first found that auranofin (AF), a coordinated gold compound, induced a significant level of cell cycle arrest at G1 phase and subsequent apoptosis of myeloma cells. Further, AF inhibited constitutive and IL-6-induced activation of JAK2 and phosphorylation of STAT3 followed by the decreased expression of Mcl-1. AF down-regulated the activation of NF-κB, and the combination of AF and a specific NF-κB inhibitor resulted in a marked decrease of Mcl-1 expression. These results suggest that AF inhibits both IL-6 induced-JAK/STAT pathway and NF-κB activation in myeloma cells.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Auranofin / pharmacology*
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Blotting, Western
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Cell Cycle / drug effects
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Cell Line, Tumor
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Down-Regulation
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Enzyme-Linked Immunosorbent Assay
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Gene Expression / drug effects
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Humans
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Multiple Myeloma / metabolism*
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Myeloid Cell Leukemia Sequence 1 Protein
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NF-kappa B / drug effects
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NF-kappa B / metabolism
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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STAT3 Transcription Factor / drug effects
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STAT3 Transcription Factor / metabolism
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Signal Transduction / drug effects*
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Transfection
Substances
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Antineoplastic Agents
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Myeloid Cell Leukemia Sequence 1 Protein
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NF-kappa B
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Proto-Oncogene Proteins c-bcl-2
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STAT3 Transcription Factor
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STAT3 protein, human
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Auranofin