Biologic activity of triptolide in t(8;21) acute myeloid leukemia cells.
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.
Zhou
Gui-Sheng
GS
Laboratory of Molecular Carcinogenesis and Targeted Therapy for Cancer, Guangzhou Institute of Biomedicine and Health & State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, China.
Hu
Zheng
Z
Fang
Hai-Tong
HT
Zhang
Feng-Xiang
FX
Pan
Xiao-Fen
XF
Chen
Xiao-Qin
XQ
Hu
An-Mei
AM
Xu
Ling
L
Zhou
Guang-Biao
GB
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D053612:Janus Kinases / Q000187:drug effects / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000187:drug effects; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
C107844:AML1-ETO fusion protein, human; D018906:Antineoplastic Agents, Alkylating; D050676:Core Binding Factor Alpha 2 Subunit; D004224:Diterpenes; D004852:Epoxy Compounds; D015514:Oncogene Proteins, Fusion; D010616:Phenanthrenes; D000075142:RUNX1 Translocation Partner 1 Protein; D050791:STAT Transcription Factors; C001899:triptolide; D019009:Proto-Oncogene Proteins c-kit; D053612:Janus Kinases