Histone Deacetylase Inhibitors Activate NF-kappaB in Human Leukemia Cells

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Recent research from the United States has shed light on the mechanisms underlying histone deacetylase inhibitor (HDACI)-mediated NF-kappaB activation in human leukemia cells. The study, conducted by R.R. Rosato and colleagues from Virginia Commonwealth University, Department of Medicine, investigated the effects of LBH-589, a histone deacetylase inhibitor, on human leukemia cells. The results showed that LBH-589 induced reactive oxygen species (ROS) and DNA breaks, leading to activation of the NF-kappaB pathway.

Key Takeaways:

  • LBH-589, a histone deacetylase inhibitor, induced reactive oxygen species (ROS) and DNA breaks in human leukemia cells.
  • The NF-kappaB pathway was activated through an ATM/NEMO-related pathway, which involved the induction of ROS and DNA damage.
  • The activation of NF-kappaB led to the induction of Mn-SOD2, which eliminated ROS and reduced DNA damage and apoptosis.
  • Interference with NF-kappaB activation diminished HDACI-mediated Mn-SOD2 induction and increased ROS accumulation, DNA damage, and apoptosis.
  • The Mn-SOD2 mimetic TBAP prevented HDACI-induced ROS and NF-kappaB activation while dramatically attenuating DNA damage and cell death.
  • TRAF2 siRNA knockdown blocked TNF-alpha-but not HDACI-mediated NF-kappaB activation and lethality.
  • ATM and NEMO siRNA knockdown blocked HDACI-mediated NF-kappaB activation, resulting in diminished MnSOD2 induction and enhanced oxidative DNA damage and cell death.

Statistics:

  • 10064-77: The page numbers of the research article published in the Journal of Biological Chemistry.
  • 285(13): The volume and issue number of the Journal of Biological Chemistry where the study was published.

Sources:

  • Rosato, R.R., et al. "Histone deacetylase inhibitors activate NF-kappaB in human leukemia cells through an ATM/NEMO-related pathway." Journal of Biological Chemistry 285(13): 10064-77.
  • Leukemia Gene Therapy