Impaired activation of caspase cascade during cell death induced by newly synthesized singlet oxygen generator, 1-buthylnaphthalene-4-propionate endoperoxide.
Endoperoxides of naphthalene derivatives generate singlet oxygen under physiological conditions. Here we have synthesized a new endoperoxide of a naphthalene derivative, 1-buthylnaphthalene-4-propionate endoperoxide (BNPE), and studied its cytotoxic properties on HepG2 and HaCaT cells. BNPE induced cell death at much lower concentration than 1-methylnaphthalene-4-propionate endoperoxide (MNPE) and naphthalene dipropionate endoperoxide (NDPE). A positive correlation exists between the amount of endoperoxide incorporated into cells and its cytotoxic ability. The cytotoxic effect of BNPE was attenuated by alpha-tocopherol but not by sodium azide. In contrast, the effects of MNPE and NDPE were attenuated by both alpha-tocopherol and sodium azide. The caspase cascade in cells treated with endoperoxide was impaired. Caspase activity in a soluble protein fraction were inhibited similarly by the above three endoperoxides. These results suggest an abortive apoptotic pathway due to the suppression of caspase activation is a general feature of cell death induced by singlet oxygen.
Otsu
Kaoru
K
Environmental Preservation Center, Yamagata University, Yamagata, Japan. yootsu@med.id.yamagata-u.ac.jp
Sato
Kazuaki
K
Sato
Michihiko
M
Ono
Hideyu
H
Ohba
Yoshihiro
Y
Katagata
Yohtaro
Y
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000633:toxicity; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008054:Lipid Peroxides / Q000494:pharmacology; D009281:Naphthalenes / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010545:Peroxides / Q000494:pharmacology* / Q000633:toxicity; D011422:Propionates / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D026082:Singlet Oxygen / Q000633:toxicity*; D019810:Sodium Azide / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology
C534729:1-butylnaphthalene-4-propionic acid endoperoxide; C114034:3-(4'-methyl-1'-naphthyl)propionic acid 1',4'-endoperoxide; D000975:Antioxidants; D003603:Cytotoxins; D008054:Lipid Peroxides; D009281:Naphthalenes; D016877:Oxidants; D010545:Peroxides; D011422:Propionates; D026082:Singlet Oxygen; D019810:Sodium Azide; D020169:Caspases; D024502:alpha-Tocopherol