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Molecular Pharmacology

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Research ArticleArticle

Hematotoxicity of the Chinese Herbal Medicine Tripterygium wilfordii Hook f in CD34-Positive Human Bone Marrow Cells

David W. Pyatt, Yanzhu Yang, Brenda Mehos, Anh Le, Wayne Stillman and Richard D. Irons
Molecular Pharmacology March 2000, 57 (3) 512-518; DOI: https://doi.org/10.1124/mol.57.3.512
David W. Pyatt
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Yanzhu Yang
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Brenda Mehos
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Anh Le
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Abstract

T2, a chloroform/methanol extract of the herbTripterygium wilfordii Hook f, has been used in China for the treatment of autoimmune and inflammatory diseases for many years. Recent experimental evidence has confirmed that T2 has potent anti-inflammatory and immunosuppressive activity, and a United States Food and Drug Administration-approved clinical trial is currently exploring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro effects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our results demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic growth factors. The inhibition of colony formation by T2 is not the result of direct cytotoxicity or increased apoptosis and indicates a functional suppression of hematopoiesis. Additional experiments demonstrate that T2 also alters transcriptional regulation in bone marrow cells by inhibiting nuclear factor-κB. This transcription factor is found in CD34+ bone marrow cells and has been recently shown to be a requirement for colony formation. These results demonstrate that therapeutic concentrations of T2 exert a significant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-κB may play a role in the blood dyscrasias encountered with the use of this drug.

Footnotes

    • Received August 30, 1999.
    • Accepted November 22, 1999.
  • Send reprint requests to: Richard Irons, Ph.D., D.A.B.T., University of Colorado Health Sciences Center, 4200 E. 9th Ave., Box C238, Denver, CO. E-mail: richard.irons{at}uchsc.edu

  • This publication was made possible by Grant ES06258 from the National Institute of Environmental Health Sciences.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 57 (3)
Molecular Pharmacology
Vol. 57, Issue 3
1 Mar 2000
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Research ArticleArticle

Hematotoxicity of the Chinese Herbal Medicine Tripterygium wilfordii Hook f in CD34-Positive Human Bone Marrow Cells

David W. Pyatt, Yanzhu Yang, Brenda Mehos, Anh Le, Wayne Stillman and Richard D. Irons
Molecular Pharmacology March 1, 2000, 57 (3) 512-518; DOI: https://doi.org/10.1124/mol.57.3.512

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Research ArticleArticle

Hematotoxicity of the Chinese Herbal Medicine Tripterygium wilfordii Hook f in CD34-Positive Human Bone Marrow Cells

David W. Pyatt, Yanzhu Yang, Brenda Mehos, Anh Le, Wayne Stillman and Richard D. Irons
Molecular Pharmacology March 1, 2000, 57 (3) 512-518; DOI: https://doi.org/10.1124/mol.57.3.512
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