Sakaguchi N, Inoue M, Ogihara Y
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Biochem Pharmacol. 1998 Jun 15;55(12):1973-81. doi: 10.1016/s0006-2952(98)00041-0.
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.
没食子酸（3,4,5-三羟基苯甲酸）是一种天然存在的植物酚类物质，根据细胞系的不同，它以明显不同的方式诱导细胞死亡。流式细胞术分析和琼脂糖凝胶电泳表明，在HL-60RG细胞中观察到染色质DNA的核小体间断裂，但在dRLh-84、HeLa和PLC/PRF/5细胞中未观察到，并且没食子酸的作用与细胞周期无关。对信号转导的详细研究表明，用细胞内硫醇抗氧化剂N-乙酰-L-半胱氨酸、过氧化氢酶和细胞内钙螯合剂双（邻氨基苯氧基）-N,N,N,N'-四乙酸乙酰甲酯（BAPTA-AM）处理可防止本研究中测试的所有细胞因没食子酸诱导的细胞死亡。然而，抗坏血酸、超氧化物歧化酶、乙二醇双乙胺四乙酸（EGTA）、核酸内切酶抑制剂硫酸锌、钙调蛋白抑制剂N-（6-氨基己基）-5-氯-1-萘磺酰胺（W-7）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂二亚苯基碘鎓氯化物对细胞死亡的影响因细胞类型而异，这表明没食子酸诱导的死亡信号在不同细胞类型中是多样的，尽管过氧化氢（H2O2）等活性氧的产生和细胞内钙浓度的升高是共同需要的信号。
