Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways

Eur J Pharmacol. 2016 May 15:779:1-7. doi: 10.1016/j.ejphar.2015.11.049. Epub 2015 Nov 27.

Abstract

Aurora-B is a protein kinase that functions mainly in the attachment of the mitotic spindle to the centromere. Overexpression of Aurora-B causes unequal distribution of genetic information, creating aneuploidy cells, a hallmark of cancer. Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from a ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly, thus globally regulating gene transcription. Additionally, these HDACs can also modify non-histone proteins. Inhibition of HDACs is a potent strategy for cancer treatment. Here, we report that inhibition of Aurora-B and HDAC exerts similar tumor suppressive effects in cells. Knockdown of Aurora-B or inhibition of HDAC achieved the same effect on repression of cell proliferation. Furthermore, we found that the tumor suppressive effect of Aurora-B and HDAC inhibition is due to the induction of cell cycle arrest and/or apoptosis. Mechanistically, we demonstrated that Aurora-B and HDAC can cooperatively regulate AKT, mTOR and Notch pathways.

Keywords: Apoptosis; Aurora-B; Cell cycle; Histone deacetylase; lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Aurora Kinase B / deficiency
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Knockdown Techniques
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / metabolism*
  • Humans
  • Jurkat Cells
  • Lymphoma / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Histone Deacetylase Inhibitors
  • RNA, Small Interfering
  • Receptors, Notch
  • AURKB protein, human
  • Aurora Kinase B
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Histone Deacetylases