Biologic activity of triptolide in t(8;21) acute myeloid leukemia cells

Leuk Res. 2011 Feb;35(2):214-8. doi: 10.1016/j.leukres.2010.07.013. Epub 2010 Aug 6.

Abstract

Triptolide is a compound isolated from the traditional Chinese medicinal herb Tripterygium wilfordii that shows potent anti-tumor activities, but its effects on acute myeloid leukemia with t(8;21) remain unclear. Here we report that triptolide inhibits cell proliferation and induces apoptosis in a dose- and time-dependent manner of t(8;21)-bearing Kasumi-1, SKNO-1 and CD34+ cells harvested from bone marrow samples of patients with t(8;21) leukemia. We show that triptolide triggers cleavage of the resultant AML1-ETO fusion protein of t(8;21), and causes downregulation of C-KIT followed by inhibition of JAK-STAT signaling. Triptolide downregulates p65 and inhibits the DNA-binding activity of NF-κB. Our data indicate that triptolide might be an effective agent for t(8;21) leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Chromosomes, Human, Pair 21 / genetics*
  • Chromosomes, Human, Pair 8 / genetics*
  • Core Binding Factor Alpha 2 Subunit / drug effects
  • Diterpenes / pharmacology*
  • Epoxy Compounds / pharmacology
  • Humans
  • Janus Kinases / drug effects
  • Janus Kinases / metabolism
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Oncogene Proteins, Fusion / drug effects
  • Phenanthrenes / pharmacology*
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / drug effects
  • RUNX1 Translocation Partner 1 Protein
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT Transcription Factors / drug effects
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects*

Substances

  • AML1-ETO fusion protein, human
  • Antineoplastic Agents, Alkylating
  • Core Binding Factor Alpha 2 Subunit
  • Diterpenes
  • Epoxy Compounds
  • Oncogene Proteins, Fusion
  • Phenanthrenes
  • RUNX1 Translocation Partner 1 Protein
  • STAT Transcription Factors
  • triptolide
  • Proto-Oncogene Proteins c-kit
  • Janus Kinases