title: Fenton reaction is primarily involved in a mechanism of (-)-epigallocatechin-3-gallate to induce osteoclastic cell death.
abstract: To propose candidates for the prevention or treatment of osteoporosis, we have screened compounds naturally in food for their ability to regulate the differentiation and function of osteoclasts. One of the major green tea flavonoids, (-)-epigallocatechin-3-gallate (EGCG), was found to induce apoptotic cell death of osteoclast-like multinucleated cells after 24 h treatment in a dose-dependent manner (25-100 microM), whereas osteoblasts were not affected. In the present study, we report for the first time a novel cell-death-inducing mechanism triggered by EGCG. The induction of apoptosis by EGCG was suppressed by pretreatment of catalase or calcitonin. It was also suppressed by Fe(III) and Fe(II) chelators. Furthermore, EGCG promoted the reduction of Fe(III) into Fe(II), and the combination of EGCG/Fe(III)/H(2)O(2) induced single-strand DNA breakage in a cell free system. These results indicate that the Fenton reaction is primarily involved in EGCG-induced osteoclastic cell death.
authors.affiliation: Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Wachi
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
authors.forename: Masanori
authors.initials: M
authors.lastname: Kato
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasai
authors.forename: Fuminori
authors.initials: F
authors.lastname: Takahashi
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005296:Ferrous Compounds; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases