Characterization of the interaction of doxorubicin with (poly)phosphoinositides in model systems Evidence for specific interaction with phosphatidylinositol‐monophosphate and ‐diphosphate

FEBS Letters

Demel, Rudy A.¹  van Kats, Carlos¹  Bets, Danny¹  de Kruijff, Ben²  de Wolf, Frits A.² 

[1]Centre for Biomembranes and Lipid Enzymology, State University Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands

[2]Institute of Molecular Biology and Medical Biotechnology, State University Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands

关键词: Doxorubicin;    Phosphoinositide;    Anionic phospholipid;    Drug—membrane interaction;    Membrane penetration;    Drug stacking;    EGTA;    di-(aminoethyl)-glycolether-N;    N;    N′;    N′-tetraacetic acid;    PIPES;    1;    4-piperazine-diethanesulfonic acid;    (DO)PA;    (SA)PA;    (DO)PC;    (dioleoyl or sn-1-stearoyl-2-arachidonoyl species of) phosphatidic acid;    phophatidylcholine;    PI;    (bovine brain) phosphatidylinositol;    PIP;    PIP2;    PI-4-phosphate and PI-4;    5-diphosphate;    SUV;    small unilamellar vesicles prepared by sonication;   

DOI  :  10.1016/0014-5793(91)81043-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The anticancer drug doxorubicin penetrates into Langmuir monolayers containing phosphoinositides. Upon binding of doxorubicin to phosphoinositide-containing SUV, its fluorescence is self-quenched due to self-association. As compared to other anionic phospholipids, as much as 2- to 3-fold larger effects were obtained with PIP and PIP₂, in mixtures of these lipids with DOPC. Doxorubicin competes efficiently with the non-penetrating antibiotic neomycin for binding to PIP₂. According to its penetration, specific binding of doxorubicin was half-maximal at 5–15 μM. It is likely that also in biological membranes doxorubicin binds specifically to PIP and PIP₂.

【 授权许可】

Unknown