Prooxidant action of hinokitiol: hinokitiol-iron dependent generation of reactive oxygen species.
Hinokitiol (alpha-thujaplicin, 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), one of the tropolone compounds purified from the woods of Chamaecyparis and Thujopsis (hinoki and hiba), produced reactive oxygen species as a complex with transition metals. Hinokitiol/iron complex inactivated aconitase, the most sensitive enzyme to reactive oxygen, whereas it did not affect aldolase and glyceraldehyde 3-phosphate dehydrogenase. The inactivation of aconitase was iron-dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species and superoxide dismutase, suggesting that the hinokitiol/iron-mediated generation of superoxide anion is responsible for the inactivation of aconitase. Addition of hinokitiol effectively enhanced the ascorbate/copper-mediated formation of 8-hydroxy-2'-deoxyguanosine in DNA. Cytotoxic effect of hinokitiol can be explained by its prooxidant properties: hinokitiol/transition metal complex generates reactive oxygen species causing inactivation of aconitase and production of hydroxyl radical resulting in the formation of DNA base adduct.
Murakami
Keiko
K
Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Ohara
Yoshihiro
Y
Haneda
Miyako
M
Tsubouchi
Ryoko
R
Yoshino
Masataka
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001205:Ascorbic Acid; D019327:Copper Sulfate; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005296:Ferrous Compounds; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015003:Yeasts / Q000201:enzymology
D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D005296:Ferrous Compounds; D039821:Monoterpenes; D016877:Oxidants; D017382:Reactive Oxygen Species; C020748:ferrous sulfate; D014334:Tropolone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C427203:calf thymus DNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005634:Fructose-Bisphosphate Aldolase; D000154:Aconitate Hydratase; D003849:Deoxyguanosine; D019327:Copper Sulfate; D001205:Ascorbic Acid; C009479:beta-thujaplicin