Stellettin A induces oxidative stress and apoptosis in HL-60 human leukemia and LNCaP prostate cancer cell lines

J Nat Prod. 2006 Jun;69(6):934-7. doi: 10.1021/np058122y.

Abstract

The present study has demonstrated a differential cytotoxicity of stellettin A (1) between human leukemia HL-60 cells (IC50 0.4 microg/mL) and human prostate cancer LNCaP cells (IC50 120 microg/mL). Treatment of cells with 1 revealed the activation of NADPH oxidase, the dramatic generation of reactive oxygen species, and the dissipation of mitochondrial membrane potentials, with HL-60 cells being more sensitive than LNCaP cells by an order of magnitude. Immunoblotting analysis further demonstrated a stronger upregulation of the apoptosis marker proteins, FasL and caspase-3, in HL-60 cells, and pretreatment of cells with antisense oligonucleotide for caspase-3 abolished apoptosis. All available evidence suggests that 1 induces oxidative cell death through a FasL-caspase-3-apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Fas Ligand Protein
  • HL-60 Cells
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Potentials
  • Mitochondria / physiology
  • Oxidative Stress / drug effects*
  • Porifera / chemistry
  • Prostatic Neoplasms / metabolism
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factors / metabolism

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Triterpenes
  • Tumor Necrosis Factors
  • stellettin A
  • CASP3 protein, human
  • Caspase 3
  • Caspases