Pentoxifylline as a modulator of anticancer drug doxorubicin. Part I: Reduction of doxorubicin DNA binding

Grzegorz Gołuński , Agnieszka Borowik , Dariusz Wyrzykowski , Anna Woziwodzka , Jacek Piosik

Abstract

Pentoxifylline – biologically active aromatic compound – has a well established capability to sequester aromatic ligands, such as an anticancer drug – doxorubicin – in mixed stacking aggregates. Formation of such hetero-complexes may influence biological activity of secluded drug. Presented work shows assessment of pentoxifylline influence on doxorubicin direct interactions with DNA employing biophysical methods. Achievement of this goal required statistical-thermodynamical model allowing numerical four-parameter analysis of experimental mixture – an issue that was successfully tackled by merging McGhee – von Hippel and Kapuscinski – Kimmel models. Results obtained with new model are well in agreement with data obtained with separate experiments with each of these two models and show reduction of doxorubicin in free (monomeric, dimeric) and complexed with DNA forms in favor of doxorubicin-pentoxifylline complexes with increasing pentoxifylline concentration. Developed model appears to be a universal tool allowing numerical analysis of mixtures containing self-aggregating ligand, DNA, and modulating agent.
Author Grzegorz Gołuński (IFB)
Grzegorz Gołuński,,
- Intercollegiate Faculty of Biotechnology UG
, Agnieszka Borowik (IFB)
Agnieszka Borowik,,
- Intercollegiate Faculty of Biotechnology UG
, Dariusz Wyrzykowski (FCh / DGICh / LPCC)
Dariusz Wyrzykowski,,
- Laboratory of Physicochemistry of Coordination Complexes
, Anna Woziwodzka (IFB / M020 / DMCB)
Anna Woziwodzka,,
- Department of Molecular and Cellular Biology
, Jacek Piosik (IFB / M020 / DMCB)
Jacek Piosik,,
- Department of Molecular and Cellular Biology
Journal seriesChemico-Biological Interactions, ISSN 0009-2797, (A 30 pkt)
Issue year2015
Vol242
Pages291-298
Publication size in sheets0.5
Keywords in Englishstacking complexes, de-intercalation, hetero-aggregation
DOIDOI:10.1016/j.cbi.2015.10.008
URL http://dx.doi.org/10.1016/j.cbi.2015.10.008
Languageen angielski
Score (nominal)30
ScoreMinisterial score = 25.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2015 = 2.618 (2) - 2015=2.935 (5)
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