Inhibition of apoptosis by menadione on exposure to UVA.
Quinones are widely distributed in the environment, both as natural products and as pollutants. This paper reports that one of the simplest quinones, 2-methyl-1,4-naphthoquinone (menadione), effectively inhibited apoptosis in the presence of UVA. Menadione suppressed the apoptosis induced by serum depletion and cell detachment. This effect was significantly enhanced by UVA irradiation. An antioxidant, N-acetylcysteine, completely inhibited the antiapoptotic effects of both menadione itself and menadione plus UVA, and peroxidation of the cells after treatment was observed using a probe to detect the intracellular production of peroxides. By contrast, 2-hydroxy-1,4-naphtoquinone (lawsone) showed no antiapoptotic effect in the presence or absence of UVA. Lawsone is reported not to undergo the redox process that produces reactive oxygen species. These results indicated that intracellular peroxidation contributed to the antiapoptotic effects of both menadione itself and menadione plus UVA. Dysregulation of the apoptotic process is critical to carcinogenesis. The photosensitization of quinone compounds as it relates to the inhibition of apoptosis should be examined in the future.
Ibuki
Y
Y
Laboratory of Radiation Biology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka-shi, 422-8526, Japan. ibuki@u-shizuoka-ken.ac.jp
Toyooka
T
T
Goto
R
R
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D041681:NIH 3T3 Cells; D009285:Naphthoquinones / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism; D014466:Ultraviolet Rays; D024483:Vitamin K 3 / Q000494:pharmacology*
D009285:Naphthoquinones; D010545:Peroxides; D024483:Vitamin K 3; C005090:lawsone; D000111:Acetylcysteine