Green tea constituents (−)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide
Green tea and its major active constituent, (−)-epigallocatechin-3-gallate (EGCG), are in clinical trials for the prevention and treatment of several diseases such as cancer. DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complex...
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| Veröffentlicht in: | Mutagenesis 2011-07, Vol.26 (4), p.489-498 |
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| creator | López-Lázaro, Miguel Calderón-Montaño, José Manuel Burgos-Morón, Estefanía Austin, Caroline A. |
| description | Green tea and its major active constituent, (−)-epigallocatechin-3-gallate (EGCG), are in clinical trials for the prevention and treatment of several diseases such as cancer. DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complexes. Using purified topoisomerases, previous in vitro studies have shown that EGCG induces the formation of topo-DNA complexes. Because the activity of a drug on purified topoisomerases does not always represent the activity in a cell, we have used an immunofluorescence technique that allows the visualisation of topo I- and topo II-DNA complexes produced in individual cells to evaluate the activity of EGCG on both enzymes. High levels of topo I- and topo II-DNA complexes were observed in K562 leukaemia cells exposed to EGCG. Similar levels of topo I- and topo II-DNA complexes were visualised in cells treated with gallic acid (GA) (the acid part of the EGCG ester). Pyrogallol (PG) also induced topo-DNA complexes with both enzymes, therefore suggesting that the activity of EGCG and GA is mediated by their PG moieties. Catalase prevented both the cytotoxicity and the formation of topo I- and topo II-DNA complexes induced by EGCG, GA, PG and myricetin (a PG-containing flavonoid recently shown to induce topo I- and topo II-DNA complexes in cells), indicating that hydrogen peroxide mediates these activities. Hydrogen peroxide induced topo I- and topo II (α and β)-DNA complexes in a time- and dose-dependent manner. The formation of topo I- and topo II-DNA complexes in cells exposed to hydrogen peroxide correlated well with the induction of apoptosis, suggesting that the topo-DNA complexes induced at long exposure times by the compounds tested in our study may be apoptotic topo-DNA complexes. Finally, we report results suggesting that PG-containing drugs may selectively kill tumour cells by generating hydrogen peroxide. |
| doi_str_mv | 10.1093/mutage/ger006 |
| format | Article |
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DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complexes. Using purified topoisomerases, previous in vitro studies have shown that EGCG induces the formation of topo-DNA complexes. Because the activity of a drug on purified topoisomerases does not always represent the activity in a cell, we have used an immunofluorescence technique that allows the visualisation of topo I- and topo II-DNA complexes produced in individual cells to evaluate the activity of EGCG on both enzymes. High levels of topo I- and topo II-DNA complexes were observed in K562 leukaemia cells exposed to EGCG. Similar levels of topo I- and topo II-DNA complexes were visualised in cells treated with gallic acid (GA) (the acid part of the EGCG ester). Pyrogallol (PG) also induced topo-DNA complexes with both enzymes, therefore suggesting that the activity of EGCG and GA is mediated by their PG moieties. Catalase prevented both the cytotoxicity and the formation of topo I- and topo II-DNA complexes induced by EGCG, GA, PG and myricetin (a PG-containing flavonoid recently shown to induce topo I- and topo II-DNA complexes in cells), indicating that hydrogen peroxide mediates these activities. Hydrogen peroxide induced topo I- and topo II (α and β)-DNA complexes in a time- and dose-dependent manner. The formation of topo I- and topo II-DNA complexes in cells exposed to hydrogen peroxide correlated well with the induction of apoptosis, suggesting that the topo-DNA complexes induced at long exposure times by the compounds tested in our study may be apoptotic topo-DNA complexes. Finally, we report results suggesting that PG-containing drugs may selectively kill tumour cells by generating hydrogen peroxide.</description><identifier>ISSN: 0267-8357</identifier><identifier>EISSN: 1464-3804</identifier><identifier>DOI: 10.1093/mutage/ger006</identifier><identifier>PMID: 21382914</identifier><identifier>CODEN: MUTAEX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Biocatalysis - drug effects ; Biological and medical sciences ; Catalase - metabolism ; Catechin - analogs & derivatives ; Catechin - chemistry ; Catechin - pharmacology ; Cell Death - drug effects ; Cell Line ; DNA - metabolism ; DNA Topoisomerases, Type I - metabolism ; DNA Topoisomerases, Type II - metabolism ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Fundamental and applied biological sciences. Psychology ; Gallic Acid - chemistry ; Gallic Acid - pharmacology ; Humans ; Hydrogen Peroxide - pharmacology ; Mice ; Models, Biological ; Molecular and cellular biology ; Molecular genetics ; Mutagenesis. Repair ; Pyrogallol - chemistry ; Pyrogallol - pharmacology ; Tea - chemistry ; Time Factors</subject><ispartof>Mutagenesis, 2011-07, Vol.26 (4), p.489-498</ispartof><rights>The Author 2011. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-a355daa0fca1ded1bb45cda675d03a60d649a0285c82000eb84a99ae6f8c06e33</citedby><cites>FETCH-LOGICAL-c426t-a355daa0fca1ded1bb45cda675d03a60d649a0285c82000eb84a99ae6f8c06e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24343578$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21382914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>López-Lázaro, Miguel</creatorcontrib><creatorcontrib>Calderón-Montaño, José Manuel</creatorcontrib><creatorcontrib>Burgos-Morón, Estefanía</creatorcontrib><creatorcontrib>Austin, Caroline A.</creatorcontrib><title>Green tea constituents (−)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide</title><title>Mutagenesis</title><addtitle>Mutagenesis</addtitle><description>Green tea and its major active constituent, (−)-epigallocatechin-3-gallate (EGCG), are in clinical trials for the prevention and treatment of several diseases such as cancer. DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complexes. Using purified topoisomerases, previous in vitro studies have shown that EGCG induces the formation of topo-DNA complexes. Because the activity of a drug on purified topoisomerases does not always represent the activity in a cell, we have used an immunofluorescence technique that allows the visualisation of topo I- and topo II-DNA complexes produced in individual cells to evaluate the activity of EGCG on both enzymes. High levels of topo I- and topo II-DNA complexes were observed in K562 leukaemia cells exposed to EGCG. Similar levels of topo I- and topo II-DNA complexes were visualised in cells treated with gallic acid (GA) (the acid part of the EGCG ester). Pyrogallol (PG) also induced topo-DNA complexes with both enzymes, therefore suggesting that the activity of EGCG and GA is mediated by their PG moieties. Catalase prevented both the cytotoxicity and the formation of topo I- and topo II-DNA complexes induced by EGCG, GA, PG and myricetin (a PG-containing flavonoid recently shown to induce topo I- and topo II-DNA complexes in cells), indicating that hydrogen peroxide mediates these activities. Hydrogen peroxide induced topo I- and topo II (α and β)-DNA complexes in a time- and dose-dependent manner. The formation of topo I- and topo II-DNA complexes in cells exposed to hydrogen peroxide correlated well with the induction of apoptosis, suggesting that the topo-DNA complexes induced at long exposure times by the compounds tested in our study may be apoptotic topo-DNA complexes. Finally, we report results suggesting that PG-containing drugs may selectively kill tumour cells by generating hydrogen peroxide.</description><subject>Animals</subject><subject>Biocatalysis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Catalase - metabolism</subject><subject>Catechin - analogs & derivatives</subject><subject>Catechin - chemistry</subject><subject>Catechin - pharmacology</subject><subject>Cell Death - drug effects</subject><subject>Cell Line</subject><subject>DNA - metabolism</subject><subject>DNA Topoisomerases, Type I - metabolism</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gallic Acid - chemistry</subject><subject>Gallic Acid - pharmacology</subject><subject>Humans</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Mice</subject><subject>Models, Biological</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Mutagenesis. Repair</subject><subject>Pyrogallol - chemistry</subject><subject>Pyrogallol - pharmacology</subject><subject>Tea - chemistry</subject><subject>Time Factors</subject><issn>0267-8357</issn><issn>1464-3804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURS0EokNhyRZ5gzpdmNqx4yTLaijDSBVsYB292C9ToyQOdiJ1_oA1v8Sf8CV4mgEkNqys93R87326hLwU_I3glbzq5wn2eLXHwLl-RFZCacVkydVjsuKZLlgp8-KMPIvxC-eiyDR_Ss4yIcusEmpFfmwD4kAnBGr8ECc3zThMka5_fvt-yXB0e-g6b2BCc-cGJtlxThNd32w320sKg6XHlTMUjLPUDXY2SCc_ehd9jwEi0h174P5Z7tjbD9fJtR87vMeYvlKDXRdpj9YlC0ubAx0PwT9E6NgibendwaZdCj1i8PfO4nPypIUu4ovTe04-v7v5tHnPbj9ud5vrW2ZUpicGMs8tAG8NCItWNI3KjQVd5JZL0NxqVQHPytyUGeccm1JBVQHqtjRco5Tn5GLRHYP_OmOc6t7FY2QY0M-xrnghCpWXOpFsIU3wMQZs6zG4HsKhFrw-1lYvtdVLbYl_dVKem3T9H_p3Twl4fQIgGujaAINx8S-npEo1l4lbL5yfx_94_gJBnLSv</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>López-Lázaro, Miguel</creator><creator>Calderón-Montaño, José Manuel</creator><creator>Burgos-Morón, Estefanía</creator><creator>Austin, Caroline A.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20110701</creationdate><title>Green tea constituents (−)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide</title><author>López-Lázaro, Miguel ; Calderón-Montaño, José Manuel ; Burgos-Morón, Estefanía ; Austin, Caroline A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-a355daa0fca1ded1bb45cda675d03a60d649a0285c82000eb84a99ae6f8c06e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Biocatalysis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Catalase - metabolism</topic><topic>Catechin - analogs & derivatives</topic><topic>Catechin - chemistry</topic><topic>Catechin - pharmacology</topic><topic>Cell Death - drug effects</topic><topic>Cell Line</topic><topic>DNA - metabolism</topic><topic>DNA Topoisomerases, Type I - metabolism</topic><topic>DNA Topoisomerases, Type II - metabolism</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gallic Acid - chemistry</topic><topic>Gallic Acid - pharmacology</topic><topic>Humans</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Mice</topic><topic>Models, Biological</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Mutagenesis. Repair</topic><topic>Pyrogallol - chemistry</topic><topic>Pyrogallol - pharmacology</topic><topic>Tea - chemistry</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>López-Lázaro, Miguel</creatorcontrib><creatorcontrib>Calderón-Montaño, José Manuel</creatorcontrib><creatorcontrib>Burgos-Morón, Estefanía</creatorcontrib><creatorcontrib>Austin, Caroline A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Mutagenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>López-Lázaro, Miguel</au><au>Calderón-Montaño, José Manuel</au><au>Burgos-Morón, Estefanía</au><au>Austin, Caroline A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Green tea constituents (−)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide</atitle><jtitle>Mutagenesis</jtitle><addtitle>Mutagenesis</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>26</volume><issue>4</issue><spage>489</spage><epage>498</epage><pages>489-498</pages><issn>0267-8357</issn><eissn>1464-3804</eissn><coden>MUTAEX</coden><abstract>Green tea and its major active constituent, (−)-epigallocatechin-3-gallate (EGCG), are in clinical trials for the prevention and treatment of several diseases such as cancer. DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complexes. Using purified topoisomerases, previous in vitro studies have shown that EGCG induces the formation of topo-DNA complexes. Because the activity of a drug on purified topoisomerases does not always represent the activity in a cell, we have used an immunofluorescence technique that allows the visualisation of topo I- and topo II-DNA complexes produced in individual cells to evaluate the activity of EGCG on both enzymes. High levels of topo I- and topo II-DNA complexes were observed in K562 leukaemia cells exposed to EGCG. Similar levels of topo I- and topo II-DNA complexes were visualised in cells treated with gallic acid (GA) (the acid part of the EGCG ester). Pyrogallol (PG) also induced topo-DNA complexes with both enzymes, therefore suggesting that the activity of EGCG and GA is mediated by their PG moieties. Catalase prevented both the cytotoxicity and the formation of topo I- and topo II-DNA complexes induced by EGCG, GA, PG and myricetin (a PG-containing flavonoid recently shown to induce topo I- and topo II-DNA complexes in cells), indicating that hydrogen peroxide mediates these activities. Hydrogen peroxide induced topo I- and topo II (α and β)-DNA complexes in a time- and dose-dependent manner. The formation of topo I- and topo II-DNA complexes in cells exposed to hydrogen peroxide correlated well with the induction of apoptosis, suggesting that the topo-DNA complexes induced at long exposure times by the compounds tested in our study may be apoptotic topo-DNA complexes. Finally, we report results suggesting that PG-containing drugs may selectively kill tumour cells by generating hydrogen peroxide.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21382914</pmid><doi>10.1093/mutage/ger006</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Biocatalysis - drug effects Biological and medical sciences Catalase - metabolism Catechin - analogs & derivatives Catechin - chemistry Catechin - pharmacology Cell Death - drug effects Cell Line DNA - metabolism DNA Topoisomerases, Type I - metabolism DNA Topoisomerases, Type II - metabolism Flavonoids - chemistry Flavonoids - pharmacology Fundamental and applied biological sciences. Psychology Gallic Acid - chemistry Gallic Acid - pharmacology Humans Hydrogen Peroxide - pharmacology Mice Models, Biological Molecular and cellular biology Molecular genetics Mutagenesis. Repair Pyrogallol - chemistry Pyrogallol - pharmacology Tea - chemistry Time Factors |
| title | Green tea constituents (−)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide |
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