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Characterization of the interaction of doxorubicin with (poly)phosphoinositides in model systems Evidence for specific interaction with phosphatidylinositol‐monophosphate and ‐diphosphate
Author(s) -
de Wolf Frits A.,
Demel Rudy A.,
Bets Danny,
van Kats Carlos,
de Kruijff Ben
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)81043-8
Subject(s) - doxorubicin , phosphatidylinositol , chemistry , biophysics , neomycin , membrane , biochemistry , binding site , antibiotics , biology , signal transduction , genetics , chemotherapy
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 PIP 2 , in mixtures of these lipids with DOPC. Doxorubicin competes efficiently with the non‐penetrating antibiotic neomycin for binding to PIP 2 . 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 PIP 2 .