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.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Alkylating / pharmacology*
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Apoptosis / drug effects*
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Blotting, Western
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Cell Proliferation / drug effects*
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Cells, Cultured
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Chromosomes, Human, Pair 21 / genetics*
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Chromosomes, Human, Pair 8 / genetics*
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Core Binding Factor Alpha 2 Subunit / drug effects
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Diterpenes / pharmacology*
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Epoxy Compounds / pharmacology
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Humans
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Janus Kinases / drug effects
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Janus Kinases / metabolism
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Leukemia, Myeloid, Acute / genetics*
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Leukemia, Myeloid, Acute / metabolism
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Oncogene Proteins, Fusion / drug effects
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Phenanthrenes / pharmacology*
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Proto-Oncogene Proteins c-kit / biosynthesis
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Proto-Oncogene Proteins c-kit / drug effects
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RUNX1 Translocation Partner 1 Protein
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Reverse Transcriptase Polymerase Chain Reaction
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STAT Transcription Factors / drug effects
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STAT Transcription Factors / metabolism
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Signal Transduction / drug effects*
Substances
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AML1-ETO fusion protein, human
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Antineoplastic Agents, Alkylating
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Core Binding Factor Alpha 2 Subunit
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Diterpenes
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Epoxy Compounds
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Oncogene Proteins, Fusion
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Phenanthrenes
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RUNX1 Translocation Partner 1 Protein
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STAT Transcription Factors
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triptolide
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Proto-Oncogene Proteins c-kit
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Janus Kinases