Pentoxifylline as a modulator of anticancer drug doxorubicin. Part I: Reduction of doxorubicin DNA binding.
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.
Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822, Gdańsk, Poland.
Grzegorz
G
Gołuński
Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822, Gdańsk, Poland.
Agnieszka
A
Borowik
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
Dariusz
D
Wyrzykowski
Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822, Gdańsk, Poland. Electronic address: anna.woziwodzka@biotech.ug.edu.pl.
Anna
A
Woziwodzka
Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822, Gdańsk, Poland. Electronic address: piosik@biotech.ug.edu.pl.
Jacek
J
Piosik
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D010431:Pentoxifylline / Q000494:pharmacology*; D013816:Thermodynamics
D000970:Antineoplastic Agents; D004317:Doxorubicin; D004247:DNA; D010431:Pentoxifylline
De-intercalation; Hetero-aggregation; Stacking complexes