Genistein induces apoptosis in immature human thymocytes by inhibiting topoisomerase-II

Biochem Biophys Res Commun. 1993 Jul 30;194(2):944-50. doi: 10.1006/bbrc.1993.1912.

Abstract

The toxicity of genistein, an inhibitor of tyrosine kinases and topoisomerase-II, on human thymocytes was investigated. Genistein induced marked chromatin fragmentation indicative of apoptosis in human thymocyte cultures. Genistein-induced thymocyte apoptosis is unlikely due to an inhibition of basal tyrosine kinase activity, since another tyrosine kinase inhibitor, herbimycin A, does not induce thymocyte apoptosis, whereas other topoisomerase-II inhibitors do. The thymocyte subpopulation most sensitive to genistein-induced apoptosis exhibited a CD3-CD4+CD8+ phenotype. This subpopulation of thymocytes is also sensitive to glucocorticoid-induced apoptosis; however, differences between genistein- and glucocorticoid-induced apoptosis were noted. In particular, unlike glucocorticoid-induced apoptosis, genistein-induced apoptosis does not involve changes in [Ca2+]i and cannot be blocked by activation of protein kinase C.

MeSH terms

  • Apoptosis / drug effects*
  • Benzoquinones
  • Cells, Cultured
  • Chromatin / drug effects
  • Chromatin / ultrastructure
  • DNA Damage*
  • Etoposide / pharmacology
  • Genistein
  • Humans
  • Immunophenotyping
  • Infant
  • Isoflavones / pharmacology*
  • Kinetics
  • Lactams, Macrocyclic
  • Methylprednisolone / pharmacology
  • Novobiocin / pharmacology
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinones / pharmacology
  • Rifabutin / analogs & derivatives
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects
  • Thymus Gland / enzymology
  • Time Factors
  • Topoisomerase II Inhibitors*

Substances

  • Benzoquinones
  • Chromatin
  • Isoflavones
  • Lactams, Macrocyclic
  • Quinones
  • Topoisomerase II Inhibitors
  • Novobiocin
  • Rifabutin
  • Phorbol 12,13-Dibutyrate
  • Etoposide
  • herbimycin
  • Genistein
  • Protein-Tyrosine Kinases
  • Tetradecanoylphorbol Acetate
  • Methylprednisolone