Deamino-hydroxy-phoslactomycin B, a biosynthetic precursor of phoslactomycin, induces myeloid differentiation in HL-60 cells

Biochem Biophys Res Commun. 2009 Jun 12;383(4):406-10. doi: 10.1016/j.bbrc.2009.04.014. Epub 2009 Apr 11.

Abstract

During the screening for novel differentiation inducers, we found that a culture broth of Streptomyces sp. HK-803 induced myeloid differentiation of HL-60 cells. The active substance was identified as deamino-hydroxy-phoslactomycin B (HPLM) by mass spectrometry, and synthesized HPLM also induced the differentiation of HL-60 cells. HPLM showed greater inhibition of protein phosphatase 2A (PP2A) activity than phoslactomycin B (PLMB); however, PLMB and okadaic acid did not induce differentiation. Moreover, treatment with ATRA and 1alpha, 25(OH)2D3 induced retinoic acid receptor-beta and 1alpha, 25(OH)2D3 24-hydroxylase, respectively, whereas HPLM did not, suggesting that HPLM is a novel differentiation inducer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • HL-60 Cells
  • Humans
  • Lactones / metabolism
  • Myeloid Cells / cytology
  • Myeloid Cells / drug effects*
  • Organophosphorus Compounds / metabolism
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Pyrones / chemistry
  • Pyrones / metabolism
  • Pyrones / pharmacology*
  • Streptomyces / chemistry
  • Streptomyces / metabolism

Substances

  • Lactones
  • Organophosphorus Compounds
  • Pyrones
  • deamino-hydroxy-phoslactomycin B
  • phoslactomycin B
  • Protein Phosphatase 2