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

The present study has demonstrated a differential cytotoxicity of stellettin A (1) between human leukemia HL-60 cells (IC50 0.4 mu g/mL) and human prostate cancer LNCaP cells (IC50 120 mu g/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.