Selective displacement of nuclear proteins by antitumor drugs having affinity for nucleic acids Journal Article

   


Authors: Bartkowiak, J.; Kapuscinski, J.; Melamed, M. R.; Darzynkiewicz, Z.
Article Title: Selective displacement of nuclear proteins by antitumor drugs having affinity for nucleic acids
Abstract: The nuclear chromatin binding sites of the antitumor drugs mitoxantrone, ametantrone, doxorubicin, mithramycin, and actinomycin D and the intercalating ligand ethidium were studied by polyacrylamide gel electrophoresis of the proteins released from rat liver nuclei in the presence and absence of these drugs in buffer of low ionic strength (10 mM NaCl). At 25-50 μM free ligand concentration, each drug produced a specific and reproducible pattern of extractable proteins of different molecular weight by (i) releasing new proteins, (ii) altering the quality of particular extracted proteins, and/or (iii) selectively entrapping other proteins in the nuclei. Ethidium, up to 100 μM, did not affect release of proteins from the nuclei. These results indicate that each ligand either has different binding site(s) in chromatin or modulates chromatin structure in a specific way by changing the affinity of different sets of proteins for their respective binding sites, resulting in their selective extraction or entrapment. The lack of effect of ethidium indicates that intercalation of the ligand to DNA, per se, does not alter the release of nuclear proteins. If patterns of nuclear proteins selectively released or retained by antitumor drugs are found to correlate with biological activity, this type of analysis may be helpful in new drug design and screening.
Keywords: doxorubicin; nuclear protein; mitoxantrone; dactinomycin; binding site; ethidium bromide; binding kinetics; priority journal; drug dna interaction; ametantrone
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 86
Issue: 13
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1989-07-01
Start Page: 5151
End Page: 5154
Language: English
DOI: 10.1073/pnas.86.13.5151
PUBMED: 2525781
PROVIDER: scopus
PMCID: PMC297575
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0038640518&doi=10.1073%2fpnas.86.13.5151&partnerID=40&md5=2f85b3403b9480574ff771d357cb6cb3
Notes: Article -- Export Date: 14 April 2020 -- Source: Scopus
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MSK Authors
  1. Myron Melamed
    148 Melamed
  2. Zbigniew Darzynkiewicz
    61 Darzynkiewicz
  3. Jan Kapuscinski
    17 Kapuscinski
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