Abstract
There is a continuous search for new therapeutic targets for treatment of multiple myeloma (MM). Here we investigated the mechanisms involved in cAMP-induced apoptosis of human MM cells. cAMP-increasing agents rapidly inhibited activation of JAK1 and its substrate STAT3. In line with STAT3 being a regulator of Mcl-1 transcription, the expression of this pro-survival factor was rapidly and selectively reduced. Notably, exogenous interleukin-6 neither prevented the inhibition of JAK1/STAT3 nor the death of MM cells induced by cAMP. Our results suggest that cAMP-mediated killing of MM cells involves inhibition of the JAK/STAT pathway, making the cAMP-pathway a promising target for treatment of MM.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Cell Line, Tumor
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Colforsin / pharmacology*
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Cyclic AMP / metabolism*
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Down-Regulation
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Humans
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Interleukin-6 / pharmacology
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Janus Kinase 1 / antagonists & inhibitors
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Janus Kinase 1 / metabolism
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Multiple Myeloma / drug therapy*
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Multiple Myeloma / metabolism
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Syndecan-1 / metabolism
Substances
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Interleukin-6
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Myeloid Cell Leukemia Sequence 1 Protein
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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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Syndecan-1
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Colforsin
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Cyclic AMP
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JAK1 protein, human
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Janus Kinase 1