Thyrsiferyl 23-acetate and its derivatives induce apoptosis in various T- and B-leukemia cells

Bioorg Med Chem. 1999 Feb;7(2):381-7. doi: 10.1016/s0968-0896(98)00226-0.

Abstract

Thyrsiferyl 23-acetate (TF-23A), a cytotoxic compound from marine red alga, induced a rapid cell death in various leukemic T- and B-cell lines. During incubation of Jurkat cells with TF-23A, condensation and fragmentation of nuclei occurred and clusters composed of uneven small cellular particles were formed. Concentration- and time-dependent DNA fragmentation was also induced by the incubation of the cells with TF-23A. These results demonstrate that the TF-23A-induced cell death follows a typical apoptotic process. The TF-23A-induced apoptosis was prevented by fetal calf serum and insulin, but not by EGF or PDGF. TF-23A and its several analogous compounds showed apoptosis-inducing activity. However, only TF-23A out of these compounds showed an inhibitory activity for protein phosphatase 2A, PP2A. These results strongly suggest that a structure of TF-23A involved in induction of apoptosis is different from that involved in the PP2A inhibition.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • B-Lymphocytes / drug effects*
  • Blotting, Western
  • Cell Line
  • Cell Survival
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Electrophoresis, Agar Gel
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • HL-60 Cells
  • Humans
  • Insulin / pharmacology
  • Jurkat Cells
  • K562 Cells
  • Mice
  • Microscopy, Phase-Contrast
  • Models, Chemical
  • Phorbol Esters / pharmacology
  • Phosphoprotein Phosphatases / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Phosphatase 2
  • Pyrans / pharmacology*
  • T-Lymphocytes / drug effects*
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Insulin
  • Phorbol Esters
  • Platelet-Derived Growth Factor
  • Pyrans
  • Epidermal Growth Factor
  • thyrsiferyl 23-acetate
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2