REACTIVE OXYGEN SPECIES AND INTRACELLULAR CA2+, COMMON SIGNALS FOR APOPTOSIS INDUCED BY GALLIC ACID

Gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plan t phenol, induces cell death in apparently different manners, dependin g on cell lines. Flow cytometric analysis and agarose gel electrophore sis indicated that internucleosomal breakdown of chromatin DNA was obs erved 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 de tailed study of signal transduction revealed that the gallic acid-indu ced cell death of all cells tested in this study was prevented by trea tment with the intracellular thiol antioxidant N-acetyl L-cysteine, ca talase, and the intracellular calcium chelator bis-(o-aminophenoxy)-N, N,N,N'-tetraaceti acid acetoxymethyl ester (BAPTA-AM). However, the ef fects of ascorbic acid, superoxide dismutase, EGTA, the endonuclease i nhibitor zinc sulfate, the calmodulin inhibitor N-(6-aminohexyl)-5-chl oro-1-naphthalenesulfonamide (W-7), and the NADPH oxidase inhibitor di phenyleneiodonium chloride on cell death were different depending on t he cell type, suggesting that the death signal induced by gallic acid was diverse among different cell types, although the production of rea ctive oxygen species, such as H2O2, and the elevation of intracellular calcium concentration were required as common signals. BIOCHEM PHARMA COL 55;12:1973-1981, 1998. (C) 1998 Elsevier Science Inc.