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 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.
Liu
W K
WK
Department of Anatomy and School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China. ken-liu@cuhk.edu.hk
Cheung
F W K
FW
Che
Chun-Tao
CT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011161:Porifera / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014315:Triterpenes; D048069:Tumor Necrosis Factors; C091312:stellettin A; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases