Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Reactive oxygen species and intracellular Ca2+, common signals for apoptosis induced by gallic acid. 971 17

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 IC50s ranging from 2.9 to 114.4 microM, 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 Ca2+ chelator, bis-(o-aminophenoxy)-N,N,N,N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), calmodulin inhibitor, W-7, and the Ca2+/Mg2+ -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.
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PMID:Cell death-inducing activity by gallic acid derivatives. 1037 66