Polyphenol tri-vanillic ester 13c inhibits P-JAK2V617F and Bcr-Abl oncokinase expression in correlation with STAT3/STAT5 inactivation and apoptosis induction in human leukemia cells.

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.

• Authors: Anne Trécul, Franck Morceau, Anthoula Gaigneaux, Marion Orsini, Sébastien Chateauvieux, Cindy Grandjenette, Mario Dicato, Marc Diederich
• Journal: Cancer letters (Cancer Lett) Vol. 340 Issue 1 Pg. 30-42 (Oct 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23811288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• MCL1 protein, human
• MYC protein, human
• Myeloid Cell Leukemia Sequence 1 Protein
• Parabens
• Phosphoproteins
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-myc
• STAT3 Transcription Factor
• STAT3 protein, human
• STAT5 Transcription Factor
• Fusion Proteins, bcr-abl
• JAK2 protein, human
• Janus Kinase 2

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Fusion Proteins, bcr-abl (genetics, metabolism)
• Gene Expression (drug effects)
• Humans
• Janus Kinase 2 (antagonists & inhibitors, genetics, metabolism)
• K562 Cells
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukocytes, Mononuclear (drug effects, physiology)
• Mutation, Missense
• Myeloid Cell Leukemia Sequence 1 Protein (genetics, metabolism)
• Parabens (pharmacology)
• Phosphoproteins (antagonists & inhibitors, genetics, metabolism)
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Protein Processing, Post-Translational (drug effects)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• STAT3 Transcription Factor (metabolism)
• STAT5 Transcription Factor (metabolism)
• Signal Transduction