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Induction of differentiation in acute promyelocytic leukemia cells (HL-60) by the verticillin derivative Sch 52900

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Author

Summary, in English

The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, is a widely used model system to study the cellular and molecular events involved in differentiation of leukemic cells. In a screening for inducers of differentiation of HL-60 cells, cultures of Gliocladium strain 4-93 were found to produce Sch 52900, a previously isolated diketopiperazine (Chu et al,. J. Antibiotics 48, 1440-1445). Sch 52900 induced the differentation of 50-69% of HL-60 cells at concentrations of 6.8-13.6 nm as measured by nitro-blue tetrazolium chloride (NBT) reduction which was followed by apoptosis as shown by DNA fragmentation. Our results demonstrate that growth arrest and the induction of differentiation by Sch 52900 is due to the induction of the cell cycle inhibitor p21(WAF) and an inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway which leads to the activation of the transcription factor AP-1.

Publishing year

2002

Language

English

Pages

759-767

Publication/Series

Zeitschrift fuer Naturforschung. Section C: A Journal of Biosciences

Volume

57

Issue

7-8

Document type

Journal article

Publisher

Verlag der Zeitschrift für Naturforschung

Topic

  • Organic Chemistry

Keywords

  • differentiation induction
  • AP-1
  • p21(WAF)

Status

Published

ISBN/ISSN/Other

  • ISSN: 0939-5075