Etoposide Catechol Is an Oxidizable Topoisomerase II Poison
Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks th...
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| Veröffentlicht in: | Chemical research in toxicology 2013-08, Vol.26 (8), p.1156-1158 |
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| creator | Jacob, David A Gibson, Elizabeth G Mercer, Susan L Deweese, Joseph E |
| description | Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic translocations. To further analyze the characteristics of etoposide metabolites, we extend our previous analysis of etoposide quinone to the catechol. We demonstrate that the catechol is ∼2–3-fold more potent than etoposide and under oxidative reaction conditions induces high levels of double-stranded DNA cleavage. These results support a role for etoposide catechol in contributing to therapy-induced DNA damage. |
| doi_str_mv | 10.1021/tx400205n |
| format | Article |
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The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic translocations. To further analyze the characteristics of etoposide metabolites, we extend our previous analysis of etoposide quinone to the catechol. We demonstrate that the catechol is ∼2–3-fold more potent than etoposide and under oxidative reaction conditions induces high levels of double-stranded DNA cleavage. 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These results support a role for etoposide catechol in contributing to therapy-induced DNA damage.</description><subject>Catechols - chemistry</subject><subject>Catechols - metabolism</subject><subject>Catechols - toxicity</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>DNA - chemistry</subject><subject>DNA - metabolism</subject><subject>DNA Breaks, Double-Stranded - drug effects</subject><subject>DNA Topoisomerases, Type II - chemistry</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>Etoposide - chemistry</subject><subject>Etoposide - metabolism</subject><subject>Etoposide - toxicity</subject><subject>Humans</subject><subject>Oxidation-Reduction</subject><issn>0893-228X</issn><issn>1520-5010</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1Lw0AQBuBFFFurB_-A5CLoITr7lWzwVErVQKEeKngLu5sNpiTZuptA9de7pbUn5zIMPLwwL0LXGB4wEPzYbxkAAd6doDHmBGIOGE7RGERGY0LExwhdeL8GwIGn52hEqEhoOMboad7bjfV1aaKZ7I3-tE2U-0h20XJbl_WPVI2JVoHU3rbGSW-iPI_edmd3ic4q2XhzddgT9P48X81e48XyJZ9NF7GkTPRxhXlVUqVoSpVWVGJFMiF4yoROBGhgYXhWpqKUkrMEFOMUREUTyHSZyJRO0N0-d-Ps12B8X7S116ZpZGfs4IvwMqMZx4wEer-n2lnvnamKjatb6b4LDMWuq-LYVbA3h9hBtaY8yr9yArjdA6l9sbaD68KX_wT9Araabjo</recordid><startdate>20130819</startdate><enddate>20130819</enddate><creator>Jacob, David A</creator><creator>Gibson, Elizabeth G</creator><creator>Mercer, Susan L</creator><creator>Deweese, Joseph E</creator><general>American Chemical Society</general><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>20130819</creationdate><title>Etoposide Catechol Is an Oxidizable Topoisomerase II Poison</title><author>Jacob, David A ; Gibson, Elizabeth G ; Mercer, Susan L ; Deweese, Joseph E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a348t-f15fd3bb373bcb3a1b29885748c680c0444459d78daa5460b45308f3609cd6a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Catechols - chemistry</topic><topic>Catechols - metabolism</topic><topic>Catechols - toxicity</topic><topic>Cytochrome P-450 CYP3A - metabolism</topic><topic>DNA - chemistry</topic><topic>DNA - metabolism</topic><topic>DNA Breaks, Double-Stranded - drug effects</topic><topic>DNA Topoisomerases, Type II - chemistry</topic><topic>DNA Topoisomerases, Type II - metabolism</topic><topic>Etoposide - chemistry</topic><topic>Etoposide - metabolism</topic><topic>Etoposide - toxicity</topic><topic>Humans</topic><topic>Oxidation-Reduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jacob, David A</creatorcontrib><creatorcontrib>Gibson, Elizabeth G</creatorcontrib><creatorcontrib>Mercer, Susan L</creatorcontrib><creatorcontrib>Deweese, Joseph E</creatorcontrib><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>Chemical research in toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jacob, David A</au><au>Gibson, Elizabeth G</au><au>Mercer, Susan L</au><au>Deweese, Joseph E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Etoposide Catechol Is an Oxidizable Topoisomerase II Poison</atitle><jtitle>Chemical research in toxicology</jtitle><addtitle>Chem. 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| source | MEDLINE; ACS Publications |
| subjects | Catechols - chemistry Catechols - metabolism Catechols - toxicity Cytochrome P-450 CYP3A - metabolism DNA - chemistry DNA - metabolism DNA Breaks, Double-Stranded - drug effects DNA Topoisomerases, Type II - chemistry DNA Topoisomerases, Type II - metabolism Etoposide - chemistry Etoposide - metabolism Etoposide - toxicity Humans Oxidation-Reduction |
| title | Etoposide Catechol Is an Oxidizable Topoisomerase II Poison |
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