Deeper insights into the drug defense of glioma cells against hydrophobic molecules

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F16%3A10325284" target="_blank" >RIV/00216208:11110/16:10325284 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ijpharm.2016.02.042" target="_blank" >http://dx.doi.org/10.1016/j.ijpharm.2016.02.042</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpharm.2016.02.042" target="_blank" >10.1016/j.ijpharm.2016.02.042</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Deeper insights into the drug defense of glioma cells against hydrophobic molecules

Popis výsledku v původním jazyce

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 mu M 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.

Název v anglickém jazyce

Deeper insights into the drug defense of glioma cells against hydrophobic molecules

Popis výsledku anglicky

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 mu M 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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Pharmaceutics

ISSN

0378-5173

e-ISSN

—

Svazek periodika

503

Číslo periodika v rámci svazku

1-2

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

56-67

Kód UT WoS článku

000372815600007

EID výsledku v databázi Scopus

2-s2.0-84959450734