Farnesylpyridinium, an analog of isoprenoid farnesol, induces apoptosis but suppresses apoptotic body formation in human promyelocytic leukemia cells

FEBS Lett. 2002 Mar 13;514(2-3):250-4. doi: 10.1016/s0014-5793(02)02373-6.

Abstract

1-Farnesylpyridinium (FPy), an analog of isoprenoid farnesol, initially induced morphological changes similar to those of typical apoptosis in human leukemia HL-60 cells but FPy-treated cells were characterized by the absolute absence of final apoptotic events such as fragmentation into apoptotic bodies. FPy-induced cell death was considered to be apoptotic on the basis of the induction of DNA fragmentation and the protection against these events by the coaddition of a pan-caspase inhibitor. The increase in the cytoplasmic cytochrome c level supported the possibility that FPy-treated cells should have the ability to complete the entire apoptotic process ending in cell fragmentation and apoptotic body formation. At concentrations too low to induce apoptosis, FPy could suppress the induction of apoptotic body formation in HL-60 cells by typical inducers of apoptosis such as actinomycin D or anisomycin. FPy exhibited a cytochalasin-like effect on spatial arrangement of actin filament independent of its apoptosis-inducing activity.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis* / drug effects
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytochalasin B / analogs & derivatives*
  • Cytochalasin B / pharmacology
  • DNA / metabolism
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Farnesol / analogs & derivatives*
  • Farnesol / chemistry
  • Farnesol / pharmacology
  • HL-60 Cells
  • Humans
  • Inclusion Bodies / drug effects*
  • Inclusion Bodies / pathology
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Pyridinium Compounds / chemical synthesis
  • Pyridinium Compounds / pharmacology*
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Protein Synthesis Inhibitors
  • Pyridinium Compounds
  • Sesquiterpenes
  • farnesylpyridinium
  • dihydrocytochalasin B
  • Cytochalasin B
  • Farnesol
  • DNA