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Antiproliferative action of valorphin in cell cultures

J Pept Sci. 2002 Aug;8(8):438-52. doi: 10.1002/psc.402.

Abstract

The antiproliferative effects of the haemoglobin beta-chain fragment (33-39) (valorphin or VV-haemorphin-5) were studied in a panel of tumour cell lines and normal cells of different origin, using various methods of activity determination (trypan blue inclusion test, sulphorhodamine B staining, MTT staining, flow cytometry and clonogenic test). Valorphin suppressed the proliferation of tumour cells by 25%-95%, depending on the cell line. The maximal valorphin activity was detected in transformed cells of fibroblastic (L929) and epithelial (MCF-7) origin, transformed haematopoietic cells (K562, HL-60) being less sensitive. In normal cells, valorphin activity was several fold lower (10%-15%). A study of the dynamics of cell proliferation in L929 cells using a visual cell count and flow cytometry showed that valorphin induced reversible and relatively short (24 h) S-phase arrest of cell proliferation, accompanied by a reversible increase of cell size. The proliferation delay was followed by a comparatively long period of reversible resistance of the cells to the peptide (96 h) when the cells are dividing at normal rate. The same dynamics were demonstrated for A549, MCF-7 and primary murine breast carcinoma cells. On the basis of the data obtained, a pattern of regulation of cell growth by valorphin is suggested.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion / drug effects
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cell Line
  • Cell Size / drug effects
  • Clone Cells / drug effects
  • Colony-Forming Units Assay
  • Drug Resistance, Neoplasm
  • Female
  • HL-60 Cells
  • Hemoglobins / chemistry
  • Hemoglobins / pharmacology*
  • Humans
  • K562 Cells
  • Mice
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • Hemoglobins
  • Peptide Fragments