Induction of apoptosis by sodium butyrate in the human Y-79 retinoblastoma cell line.
The mode of cell death induced in the Y-79 human retinoblastoma cell line by sodium butyrate (SB), a short-chain fatty acid with potent inhibitory effects on the growth of many transformed cell lines, was investigated by fluorescence and transmission electron microscopy, agarose gel electrophoresis, and metabolic studies. While SB (< 1 mM) resulted in marked morphological differentiation, higher concentrations (1-4 mM) induced predominantly apoptotic involution in Y-79 in a concentration-dependent fashion after a latent period of 24 h. Dying cells displayed the characteristic morphology of apoptosis accompanied by DNA laddering with agarose gel electrophoresis. Extensive cell necrosis was apparent with 0.5 M SB. Induction of apoptosis and DNA laddering by SB was reduced by putative inhibitors of RNA and protein synthesis, but not putative endonuclease inhibitors. These results are important for understanding the mode of action of sodium butyrate as a potential cancer chemotherapeutic agent.
Conway
R M
RM
Department of Clinical Ophthalmology, University of Sydney, Sydney Eye Hospital, Woolloomooloo, New South Wales, Australia.
Madigan
M C
MC
Penfold
P L
PL
Billson
F A
FA
D017209:Apoptosis / Q000187:drug effects*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D005134:Eye Neoplasms; D006801:Humans; D007700:Kinetics; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D012175:Retinoblastoma; D013431:Sulfates / Q000494:pharmacology; D014048:Tolonium Chloride; D014407:Tumor Cells, Cultured; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D002087:Butyrates; D004396:Coloring Agents; D013431:Sulfates; D017967:Zinc Compounds; D020148:Butyric Acid; D014048:Tolonium Chloride; D001312:Aurintricarboxylic Acid; D019287:Zinc Sulfate