Abstract
Constitutive activity of kinases has been reported in many types of cancers, so that inhibition of "onco-kinases" became a validated anti-cancer strategy. We found that the polyphenol 13c, a tri-vanillate derivative, inhibited kinase phosphorylation in leukemia cells. P-JAK2, P-Src and P-PI3Kp85 inhibition occurred independently of phosphatase involvement in JAK2V617F expressing HEL cells while 13c inhibited Bcr-Abl expression without inhibition of phosphorylation in chronic myelogenous leukemia cell lines (K562, MEG-01). In correlation with kinase inhibition, 13c abolished constitutive P-STAT3/P-STAT5 expression, down-regulated Mcl-1 and c-Myc gene expression and induced apoptosis. Altogether, polyphenol 13c displays potential antitumor activities by affecting onco-kinases and STAT activities.
Keywords:
13c; Bcr–Abl; JAK2; Kinase; Polyphenol; STAT.
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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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism*
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Gene Expression / drug effects
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Humans
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Janus Kinase 2 / antagonists & inhibitors*
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Janus Kinase 2 / genetics
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Janus Kinase 2 / metabolism
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K562 Cells
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / physiology
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Mutation, Missense
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Myeloid Cell Leukemia Sequence 1 Protein / genetics
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Myeloid Cell Leukemia Sequence 1 Protein / metabolism
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Parabens / pharmacology*
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Phosphoproteins / antagonists & inhibitors
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Protein Processing, Post-Translational / drug effects
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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STAT3 Transcription Factor / metabolism*
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STAT5 Transcription Factor / metabolism*
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Signal Transduction
Substances
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Antineoplastic Agents
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MCL1 protein, human
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MYC protein, human
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Myeloid Cell Leukemia Sequence 1 Protein
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Parabens
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Phosphoproteins
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-myc
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT5 Transcription Factor
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Fusion Proteins, bcr-abl
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JAK2 protein, human
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Janus Kinase 2