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标题：Ca2+-Dependent Caspase Activation by Gallic Acid Derivatives
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作者：Kazuto ISUZUGAWA ; Makoto INOUE ; Yukio OGIHARA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2001
卷号：24
期号：7
页码：844-847
DOI：10.1248/bpb.24.844
出版社：The Pharmaceutical Society of Japan
摘要：Gallic acid (GA) derivatives, 3,4-methylenedioxyphenyl 3,4,5-trihydroxybenzoate (GD-1) and S-(3,4-methylenedioxyphenyl)3,4,5-trihydroxythiobenzoate (GD-3), were previously reported to induce apoptosis in tumor cells with IC₅₀s of 14.5 μM and 3.9 μM, respectively. To elucidate the mechanism by which these gallic acid derivatives (GDs) induce apoptosis, we studied whether GD-1 and GD-3 can activate caspases. When promyelocytic leukemia HL-60RG cells were treated with GD-1 and GD-3, poly(ADP-ribose)polymerase (PARP), a substrate of caspase-3, was cleaved into 85 kDa of degradative product with increasing incubation time. GA also activated PARP cleavage, which was inhibited by catalase, N-acetyl-L-cysteine (NAC), and intracellular Ca²⁺ chelator 1,2-bis(2-aminophenoxyethane)-N, N, N, N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM), in addition to a caspase inhibitor, Z-VAD-FMK. Its inhibitory pattern was identical with that of hypoxanthine/xanthine oxidase. On the other hand, GD-1 and GD-3-induced PARP cleavage was not suppressed by catalase or NAC, but by BAPTA-AM. This suggested that the GD-elicited signaling pathway is different from GA’s. Taken together, GDs activated caspase-3 following intracellular Ca²⁺ elevation independent of reactive oxygen species. Thus, it became evident that the signaling pathway leading to apoptosis was regulated by GDs in a different manner from GA.
关键词：gallic acid derivative;apoptosis;caspase;intracellular Ca2+;reactive oxygen species