title: Deeper insights into the drug defense of glioma cells against hydrophobic molecules.
abstract: By means of fluorescence microscopy the intracellular distribution of fluorescent drugs with different hydrophobicity (quinizarin, emodin and hypericin) was studied. Selective photoactivation of these drugs in precisely defined position (nuclear envelope) allowed moderately hydrophobic emodin enter the nucleus. Highly hydrophobic hypericin was predominantly kept in the membranes with no fluorescence observed in the nucleus. The redistribution of quinizarin, emodin and hypericin between lipids, proteins and DNA was studied in solutions and cells. Based on these results was proposed theoretical model of hydrophobic drugs' nuclear internalization after photo-activation. Molecular docking models showed that hypericin has the strongest affinity to P-glycoprotein involved in the cell detoxification. Presence of 10 μM quinizarin, emodin or hypericin increased P-glycoprotein function in U87 MG cells. Moreover, emodin pretreatment allowed quinizarin nuclear internalization without photo-activation, which was not the case for hypericin. The synergy of such pretreatment and photo-activation should lessen the drug doses with simultaneous increase of drug efficacy triggering cell apoptosis/necrosis.
authors.affiliation: Institute of Biophysics, University of Veterinary Medicine and Pharmacy, Komenskeho 73, 041 81 Kosice, Slovakia. Electronic address: Valeria.Verebova@uvlf.sk.
authors.forename: Valeria
authors.initials: V
authors.lastname: Verebova
authors.affiliation: Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: dominik.belej@student.upjs.sk.
authors.forename: Dominik
authors.initials: D
authors.lastname: Belej
authors.affiliation: Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: jaroslava.joniova@upjs.sk.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Joniova
authors.affiliation: Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia; Center for Interdisciplinary Biosciences, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: zuzana.jurasekova@upjs.sk.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Jurasekova
authors.affiliation: Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia; Center for Interdisciplinary Biosciences, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: pavol.miskovsky@upjs.sk.
authors.forename: Pavol
authors.initials: P
authors.lastname: Miskovsky
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: tibor.kozar@upjs.sk.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kozar
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: denis.horvath@upjs.sk.
authors.forename: Denis
authors.initials: D
authors.lastname: Horvath
authors.affiliation: Institute of Biophysics, University of Veterinary Medicine and Pharmacy, Komenskeho 73, 041 81 Kosice, Slovakia; Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, Salmovska 1, 120 00 Prague 2, Czech Republic. Electronic address: Jana.Stanicova@uvlf.sk.
authors.forename: Jana
authors.initials: J
authors.lastname: Stanicova
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: Valeria.Verebova@uvlf.sk.
authors.forename: Veronika
authors.initials: V
authors.lastname: Huntosova
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000873:Anthracenes; D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D008078:Cholesterol, LDL / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004642:Emodin / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D005910:Glioma / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D062105:Molecular Docking Simulation; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000873:Anthracenes; D000880:Anthraquinones; D008078:Cholesterol, LDL; D012709:Serum Albumin; D010569:Perylene; C004965:hypericin; C034890:1,4-dihydroxyanthraquinone; D004247:DNA; D004642:Emodin
keywords: Antraquinones; Glioma cells; Hypericin; P-glycoprotein; Selective photo-activation