Anthracyclines React with Apurinic/Apyrimidinic Sites in DNA.
Journal
ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906
Informations de publication
Date de publication:
16 06 2023
16 06 2023
Historique:
pmc-release:
16
06
2024
medline:
19
6
2023
pubmed:
18
5
2023
entrez:
18
5
2023
Statut:
ppublish
Résumé
The combination of doxorubicin (Adriamycin) and cyclophosphamide, referred to as AC chemotherapy, is commonly used for the clinical treatment of breast and other cancers. Both agents target DNA with cyclophosphamide causing alkylation damage and doxorubicin stabilizing the topoisomerase II-DNA complex. We hypothesize a new mechanism of action whereby both agents work in concert. DNA alkylating agents, such as nitrogen mustards, increase the number of apurinic/apyrimidinic (AP) sites through deglycosylation of labile alkylated bases. Herein, we demonstrate that anthracyclines with aldehyde-reactive primary and secondary amines form covalent Schiff base adducts with AP sites in a 12-mer DNA duplex, calf thymus DNA, and MDA-MB-231 human breast cancer cells treated with nor-nitrogen mustard and the anthracycline mitoxantrone. The anthracycline-AP site conjugates are characterized and quantified by mass spectrometry after NaB(CN)H
Identifiants
pubmed: 37200590
doi: 10.1021/acschembio.3c00033
pmc: PMC10391585
mid: NIHMS1920392
doi:
Substances chimiques
Anthracyclines
0
Schiff Bases
0
DNA
9007-49-2
Topoisomerase II Inhibitors
0
Doxorubicin
80168379AG
Antibiotics, Antineoplastic
0
Alkylating Agents
0
Cyclophosphamide
8N3DW7272P
DNA Adducts
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1315-1323Subventions
Organisme : NCI NIH HHS
ID : P01 CA160032
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA077598
Pays : United States
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