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

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.

• Authors: W K Liu, F W K Cheung, Chun-Tao Che
• Journal: Journal of natural products (J Nat Prod) Vol. 69 Issue 6 Pg. 934-7 (Jun 2006) ISSN: 0163-3864 [Print] United States
• PMID: 16792413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, isolation & purification, pharmacology)
• Tumor Cells, Cultured
• Tumor Necrosis Factors (metabolism)