Reactive oxygen species and intracellular Ca2+, common signals for apoptosis induced by gallic acid.
Gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, induces cell death in apparently different manners, depending on cell lines. Flow cytometric analysis and agarose gel electrophoresis indicated that internucleosomal breakdown of chromatin DNA was observed in HL-60RG cells but not in dRLh-84, HeLa, and PLC/PRF/5 cells, and that the action of gallic acid was independent of cell cycle. A detailed study of signal transduction revealed that the gallic acid-induced cell death of all cells tested in this study was prevented by treatment with the intracellular thiol antioxidant N-acetyl-L-cysteine, catalase, and the intracellular calcium chelator bis-(o-aminophenoxy)-N,N,N,N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM). However, the effects of ascorbic acid, superoxide dismutase, EGTA, the endonuclease inhibitor zinc sulfate, the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), and the NADPH oxidase inhibitor diphenyleneiodonium chloride on cell death were different depending on the cell type, suggesting that the death signal induced by gallic acid was diverse among different cell types, although the production of reactive oxygen species, such as H2O2, and the elevation of intracellular calcium concentration were required as common signals.
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
N
N
Sakaguchi
M
M
Inoue
Y
Y
Ogihara
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D005707:Gallic Acid; D002118:Calcium