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

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Abstract

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.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Organic Chemistry

Keywords

  • differentiation induction, AP-1, p21(WAF)
Original languageEnglish
Pages (from-to)759-767
JournalZeitschrift fuer Naturforschung. Section C: A Journal of Biosciences
Volume57
Issue number7-8
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)