Role of hydrogen peroxide for cell death induction by sodium 5,6-benzylidene-L-ascorbate.
The role of hydrogen peroxide in the induction of cell death in human promyelocytic leukemic HL-60 cells by sodium 5,6-benzylidene-L-ascorbate (SBA) and its degradation product, ascorbic acid, was investigated. Millimolar concentrations of these compounds induced cell death, characterized by cell shrinkage, nuclear and internucleosomal DNA fragmentation, disappearance of microvilli and condensation of chromatin near the nuclear membrane. Catalase significantly reduced the cytotoxic activity of these compounds, whereas superoxide dismutase, nitric oxide (NO) generator, NO scavenger and NO synthase inhibitor were inactive, suggesting the possible role of H2O2. Determination of H2O2 with the peroxyoxalate chemiluminescence demonstrated that sodium ascorbate and SBA produced H2O2 in amounts necessary for cell death induction.
Tajima
M
M
Department of Dental Pharmacology, Meikai University School of Dentistry, Saitama, Japan.
Toguchi
M
M
Kanda
Y
Y
Kunii
S
S
Hosaka
M
M
Arakawa
H
H
Maeda
M
M
Satoh
K
K
Asano
K
K
Kochi
M
M
Sakagami
H
H
D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D001597:Benzylidene Compounds / Q000633:toxicity*; D002374:Catalase / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D008163:Luminescent Measurements; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009707:Nucleosomes / Q000187:drug effects / Q000473:pathology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000970:Antineoplastic Agents; D000975:Antioxidants; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D006146:Guanidines; D009707:Nucleosomes; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; C004479:pimagedine; C070680:zilascorb; D019331:NG-Nitroarginine Methyl Ester