Deeper insights into the drug defense of glioma cells against hydrophobic molecules
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26940808
DOI
10.1016/j.ijpharm.2016.02.042
PII: S0378-5173(16)30147-8
Knihovny.cz E-zdroje
- Klíčová slova
- Antraquinones, Glioma cells, Hypericin, P-glycoprotein, Selective photo-activation,
- MeSH
- anthraceny MeSH
- anthrachinony chemie farmakologie účinky záření MeSH
- buněčné jádro metabolismus účinky záření MeSH
- DNA chemie MeSH
- emodin chemie farmakologie účinky záření MeSH
- gliom metabolismus MeSH
- hydrofobní a hydrofilní interakce MeSH
- LDL-cholesterol chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- P-glykoprotein metabolismus MeSH
- perylen analogy a deriváty chemie farmakologie účinky záření MeSH
- sérový albumin chemie MeSH
- simulace molekulového dockingu MeSH
- světlo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,4-dihydroxyanthraquinone MeSH Prohlížeč
- anthraceny MeSH
- anthrachinony MeSH
- DNA MeSH
- emodin MeSH
- hypericin MeSH Prohlížeč
- LDL-cholesterol MeSH
- P-glykoprotein MeSH
- perylen MeSH
- sérový albumin MeSH
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.
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