title: Pentoxifylline as a modulator of anticancer drug doxorubicin. Part II: Reduction of doxorubicin DNA binding and alleviation of its biological effects.
abstract: Anticancer drug doxorubicin is commonly used in cancer treatment. However, drug's severe side effects make toxicity reduction important matter. Another biologically active aromatic compound, pentoxifylline, can sequester aromatic compounds in stacking complexes reducing their bioactivity. This work deals with the problem of alleviating doxorubicin side effects by pentoxifylline. We employed a wide spectrum of prokaryotic and eukaryotic cellular assays. In addition, we used the doxorubicin-pentoxifylline mixed association constant to quantitatively assess pentoxifylline influence on the doxorubicin mutagenic activity. Obtained results indicate strong protective effects of pentoxifylline towards doxorubicin, observed on bacteria and human keratinocytes with no such effects observed on the cancer cells. It may be hypothesized that, considering much shorter half-life of pentoxifylline than doxorubicin, simultaneous administration of doxorubicin and pentoxifylline will lead to gradual release of doxorubicin from complexes with pentoxifylline to reach desired therapeutic concentration. Proposed results shed light on the possible doxorubicin chemotherapy modification and its side effects reduction without the loss of its therapeutic potential.
authors: Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Abrahama 58, 80-307 Gdańsk, Poland.
authors: Grzegorz
authors: G
authors: Gołuński
authors: Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Abrahama 58, 80-307 Gdańsk, Poland.
authors: Agnieszka
authors: A
authors: Borowik
authors: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology UG-MUG, Abrahama 58, 80-307 Gdańsk, Poland.
authors: Natalia
authors: N
authors: Derewońko
authors: Division of Plant Protection and Biotechnology, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdańsk, Poland; Laboratory of Human Physiology, Medical University of Gdansk, Tuwima 15, 80-210 Gdańsk, Poland.
authors: Anna
authors: A
authors: Kawiak
authors: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology UG-MUG, Abrahama 58, 80-307 Gdańsk, Poland.
authors: Michał
authors: M
authors: Rychłowski
authors: Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Abrahama 58, 80-307 Gdańsk, Poland. Electronic address: anna.woziwodzka@biotech.ug.edu.pl.
authors: Anna
authors: A
authors: Woziwodzka
authors: Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology UG-MUG, Abrahama 58, 80-307 Gdańsk, Poland. Electronic address: piosik@biotech.ug.edu.pl.
authors: Jacek
authors: J
authors: Piosik
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D018613:Microscopy, Confocal; D010431:Pentoxifylline / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D004247:DNA; D010431:Pentoxifylline
keywords: Cell cycle; Confocal microscopy; Cytotoxicity; Mutagenicity