Inhibitory effect of tellimagrandin I on chemically induced differentiation of human leukemia K562 cells

Toxicol Lett. 2004 Mar 1;147(2):109-19. doi: 10.1016/j.toxlet.2003.12.008.

Abstract

Tellimagrandin I is a hydrolysable tannin compound widely present in plants. In this study, the effect of tellimagrandin I on chemically induced erythroid and megakaryocytic differentiation was investigated using K562 cells as differentiation model. It was found that tellimagrandin I not only inhibited the hemoglobin synthesis in butyric acid (BA)- and hemin-induced K562 cells with IC50 of 3 and 40microM, respectively, but also inhibited other erythroid differentiation marker including acetylcholinesterase (AChE) and glycophorin A (GPA) in BA-induced K562 cells. Tellimagrandin I also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of CD61 protein, a megakaryocytic marker. RT-PCR analysis showed that tellimagrandin I decreased the expression of erythroid genes (gamma-globin and porphobilinogen deaminase (PBGD)) and related transcription factors (GATA-1 and NF-E2) in BA-induced K562 cells, whereas tellimagrandin I induced the overexpresison of GATA-2 transcription factor that played negative regulation on erythroid differentiation. These results indicated that tellimagrandin I had inhibitory effects on erythroid and megakaryocytic differentiation, which suggested that tannins like tellimagrandin I might influence the anti-tumor efficiency of some drugs and the hematopoiesis processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Benzidines / chemistry
  • Cell Differentiation / drug effects*
  • Cholinesterase Inhibitors / pharmacology
  • DNA Primers
  • DNA-Binding Proteins / physiology
  • Erythroid Precursor Cells / drug effects
  • Erythroid-Specific DNA-Binding Factors
  • Flow Cytometry
  • GATA1 Transcription Factor
  • GATA2 Transcription Factor
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology*
  • Glucosides / pharmacology*
  • Glycophorins / metabolism
  • Hematopoiesis / drug effects
  • Hemoglobins / biosynthesis
  • Humans
  • Hydroxymethylbilane Synthase / metabolism
  • K562 Cells
  • Megakaryocytes / drug effects
  • NF-E2 Transcription Factor
  • NF-E2 Transcription Factor, p45 Subunit
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors / physiology

Substances

  • Benzidines
  • Cholinesterase Inhibitors
  • DNA Primers
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • GATA2 Transcription Factor
  • GATA2 protein, human
  • Glucosides
  • Glycophorins
  • Hemoglobins
  • NF-E2 Transcription Factor
  • NF-E2 Transcription Factor, p45 Subunit
  • NFE2 protein, human
  • RNA, Messenger
  • Transcription Factors
  • benzidine
  • Gallic Acid
  • tellimagrandin I
  • Hydroxymethylbilane Synthase
  • Acetylcholinesterase
  • Tetradecanoylphorbol Acetate