Fenton reaction is primarily involved in a mechanism of (-)-epigallocatechin-3-gallate to induce osteoclastic cell death.
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.
Nakagawa
Hiroshi
H
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Wachi
Masaaki
M
Woo
Je-Tae
JT
Kato
Masanori
M
Kasai
Shinya
S
Takahashi
Fuminori
F
Lee
In-Seon
IS
Nagai
Kazuo
K
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
D005296:Ferrous Compounds; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases