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

Cancer Lett. 2013 Oct 28;340(1):30-42. doi: 10.1016/j.canlet.2013.06.023. Epub 2013 Jun 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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