Cell Death-Inducing Activity by Gallic Acid Derivatives
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概要
- 論文の詳細を見る
In this study, the cytotoxic activity of gallic acid derivatives (GDs) was studied using some cancer cell lines.Among them, 3,4-methylenedioxyphenyl 3,4,5-trihydroxybenzoate (GD-1) and S-(3,4-methylenedioxyphenyl)-3,4,5-trihydroxy-thiobenzoate (GD-3) were found to induce cell death in cancer cell lines with IC_<50>s ranging from 2.9 to 114.4 μM, a concentration comparable with or lower than that of gallic acid. On the other hand, although gallic acid did not show any cytotoxicity against primary cultured rat hepatocytes and human keratinocytes, GD-1 and -3 showed slightly higher sensitivity against such normal cells, when compared with gallic acid. The cell death induced by gallic acid and GD-1 was accompanied by internucleosomal DNA fragmentation characteristic of apoptosis, whereas only smear DNA degradation was detected following GD-3 treatment. When the mechanism by which GD-1 and -3 caused cell death in HL-60RG cells was examined, GD-1 and -3-induced cell death was inhibited by the intracellular Ca^<2+> chelator, bis-(o-aminophenoxy)-N, N, N, N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), calmodulin inhibitor, W-7,and the Ca^<2+>/MG^<2+>-dependent endonuclease inhibitor zinc sulfate. In contrast, catalase, N-acetylcysteine (NAC), and ascorbic acid inhibited gallic acid-induced apoptosis in HL-60RG cells, whereas they had no effect on GD-1- and -3-induced cell death. This result suggests that GD-1 and -3 induced cell death in a different manner to gallic acid. In conclusion, esterification of gallic acid with a 3,4-methylenedioxyphenyl group yielded potent agents to treat cancer with a different signaling pathway from gallic acid, although selectivity was lost.
- 公益社団法人日本薬学会の論文
- 1999-05-15
著者
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Inoue Makoto
Department of Pediatrics, Shimane Medical University
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Inoue M
Lab. Of Medicinal Resources School Of Pharmacy Aichi Gakuin Univ.
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SAKAGUCHI Nahoko
Department of Biochemistry, Nagoya University School of Medicine
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Ogihara Yukio
Laboratory Of Pharmacognosy Graduate School Of Pharmaceutical Sciences Nagoya City University
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Ogihara Yukio
Department Of Pharmacognosy Faculty Of Pharmaceutical Sciences Nogoya City University
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Ogihara Yukio
Department Of Pharmacognosy And Plant Chemistry Faculty Of Pharmaceutical Sciences Nagoya City Unive
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Ogihara Yukio
Graduate School Of Pharmaceutical Sciences Nagoya City University
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Inoue M
Laboratory Of Pharmacognosy Graduate School Of Pharmaceutical Sciences Nagoya City University
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ISUZUGAWA Kazuto
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagoya City University
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HOSAKA Kunio
Tsumura Co., Ltd.,
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Hosaka Kunio
Tsumura Co. Ltd.
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Isuzugawa Kazuto
Department Of Pharmacognosy Faculty Of Pharmaceutical Sciences Nagoya City University
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Ogihara Y
Department Of Pharmacognosy And Plant Chemistry Faculty Of Pharmaceutical Sciences Nagoya City Unive
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Sakaguchi N
Nagoya Univ. School Of Medicine Nagoya Jpn
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Sakaguchi Nahoko
Department Of Biochemistry Nagoya University School Of Medicine
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Inoue Makoto
Department Of Biological Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University
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