Deeper insights into the drug defense of glioma cells against hydrophobic molecules
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26940808
DOI
10.1016/j.ijpharm.2016.02.042
PII: S0378-5173(16)30147-8
Knihovny.cz E-resources
- Keywords
- Antraquinones, Glioma cells, Hypericin, P-glycoprotein, Selective photo-activation,
- MeSH
- Anthracenes MeSH
- Anthraquinones chemistry pharmacology radiation effects MeSH
- Cell Nucleus metabolism radiation effects MeSH
- DNA chemistry MeSH
- Emodin chemistry pharmacology radiation effects MeSH
- Glioma metabolism MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Cholesterol, LDL chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism MeSH
- Perylene analogs & derivatives chemistry pharmacology radiation effects MeSH
- Serum Albumin chemistry MeSH
- Molecular Docking Simulation MeSH
- Light MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1,4-dihydroxyanthraquinone MeSH Browser
- Anthracenes MeSH
- Anthraquinones MeSH
- DNA MeSH
- Emodin MeSH
- hypericin MeSH Browser
- Cholesterol, LDL MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- Perylene MeSH
- Serum 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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