Article ; Online: Interaction of mitoxantrone with abasic sites - DNA strand cleavage and inhibition of apurinic/apyrimidinic endonuclease 1, APE1.
2023 Volume 133, Page(s) 103606
Abstract: Mitoxantrone (1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-anthracene-9,10-dione) is a clinically-relevant synthetic anthracenedione that functions as a topoisomerase II poison by trapping DNA double-strand break intermediates. Mitoxantrone ... ...
| Abstract | Mitoxantrone (1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-anthracene-9,10-dione) is a clinically-relevant synthetic anthracenedione that functions as a topoisomerase II poison by trapping DNA double-strand break intermediates. Mitoxantrone binds to DNA via both stacking interactions with DNA bases and hydrogen bonding with the sugar-phosphate backbone. It has been shown that mitoxantrone inhibits apurinic/apyrimidinic (AP) endonuclease 1 (APE1)-catalyzed incision of DNA containing a tetrahydrofuran (THF) moiety and more recently, that mitoxantrone forms Schiff base conjugates at AP sites in DNA. In this study, mitoxantrone-mediated inhibition of APE1 at THF sites was shown to be consistent with preferential binding to, and thermal stabilization of DNA containing a THF site as compared to non-damaged DNA. Investigations into the properties of mitoxantrone at AP and 3' α,β-unsaturated aldehyde sites demonstrated that in addition to being a potent inhibitor of APE1 at these biologically-relevant substrates (∼ 0.5 μM IC |
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| MeSH term(s) | Mitoxantrone/pharmacology ; DNA/metabolism ; DNA Repair ; Aldehydes ; Phosphates ; Endonucleases/metabolism ; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism | |||||
| Chemical Substances | Mitoxantrone (BZ114NVM5P) ; DNA (9007-49-2) ; Aldehydes ; Phosphates ; Endonucleases (EC 3.1.-) ; DNA-(Apurinic or Apyrimidinic Site) Lyase (EC 4.2.99.18) | |||||
| Language | English | |||||
| Publishing date | 2023-11-20 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 2071608-4 | |||||
| ISSN | 1568-7856 ; 1568-7864 | |||||
| ISSN (online) | 1568-7856 | |||||
| ISSN | 1568-7864 | |||||
| DOI | 10.1016/j.dnarep.2023.103606 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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