Induction of Differentiation in Acute Promyelocytic Leukemia Cells (HL-60) by the Verticillin Derivative Sch 52900

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 nᴍ 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 p21WAF and an inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway which leads to the activation of the transcription factor AP-1.

• Publication year

  2002

• Venue

  Zeitschrift für Naturforschung C - A Journal of Biosciences

• Publication date

  2002-07-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1515/znc-2002-7-834PMID 12241008
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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