The relationship of doxorubicin binding to membrane lipids with drug resistance

Sanjay Awasthi; Rajendra Sharma; Yogesh C. Awasthi; James A. Belli; Eugene P. Frenkel

doi:10.1016/0304-3835(92)90060-9

The relationship of doxorubicin binding to membrane lipids with drug resistance

Sanjay Awasthi, Rajendra Sharma, Yogesh C. Awasthi, James A. Belli, Eugene P. Frenkel

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Doxorubicin (DOX, Adriamycin) binds with high affinity to cellular membranes inflicting multiple lesions which are believed to be important in DOX-mediated neoplastic cell death. Using fluorescence and radioactive [14-¹⁴C-14]DOX assays for DOX, we have measured the partitioning of DOX between the cytosolic and membrane fractions of erythrocytes and of DOX-sensitive (V-79) and resistant (LZ) Chinese hamster lung fibroblast cells. In both erythrocytes and fibroblasts, a significant fraction of DOX was associated with the membrane fraction. More significantly, the quantity of lipid-bound DOX in the fibroblasts correlated with the cell's susceptibility to DOX. The significance of these findings in the context of existing knowledge about DOX-membrane interactions is discussed.

Original language	English (US)
Pages (from-to)	109-116
Number of pages	8
Journal	Cancer Letters
Volume	63
Issue number	2
DOIs	https://doi.org/10.1016/0304-3835(92)90060-9
State	Published - Apr 15 1992

Keywords

Adriamycin
Chinese hamster lung
V-79 and LZ
[14-C]doxorubicin
anthracycline
doxorubicin
drug resistance
fibroblast cell lines
subcellular partitioning of DOX

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/0304-3835(92)90060-9

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@article{c5304f2a80ba4ef2970be1e7d4ed9d5a,

title = "The relationship of doxorubicin binding to membrane lipids with drug resistance",

abstract = "Doxorubicin (DOX, Adriamycin) binds with high affinity to cellular membranes inflicting multiple lesions which are believed to be important in DOX-mediated neoplastic cell death. Using fluorescence and radioactive [14-14C-14]DOX assays for DOX, we have measured the partitioning of DOX between the cytosolic and membrane fractions of erythrocytes and of DOX-sensitive (V-79) and resistant (LZ) Chinese hamster lung fibroblast cells. In both erythrocytes and fibroblasts, a significant fraction of DOX was associated with the membrane fraction. More significantly, the quantity of lipid-bound DOX in the fibroblasts correlated with the cell's susceptibility to DOX. The significance of these findings in the context of existing knowledge about DOX-membrane interactions is discussed.",

keywords = "Adriamycin, Chinese hamster lung, V-79 and LZ, [14-C]doxorubicin, anthracycline, doxorubicin, drug resistance, fibroblast cell lines, subcellular partitioning of DOX",

author = "Sanjay Awasthi and Rajendra Sharma and Awasthi, {Yogesh C.} and Belli, {James A.} and Frenkel, {Eugene P.}",

note = "Funding Information: This investigation was supported in part by USPHS Grants CA27967 (Y.C.A.) and CA34269 (J.A.B.) from the National Cancer Research Institute and by the Nasher Family Cancer Research Program (E.P.F.).",

year = "1992",

month = apr,

day = "15",

doi = "10.1016/0304-3835(92)90060-9",

language = "English (US)",

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pages = "109--116",

journal = "Cancer Letters",

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T1 - The relationship of doxorubicin binding to membrane lipids with drug resistance

AU - Awasthi, Sanjay

AU - Sharma, Rajendra

AU - Awasthi, Yogesh C.

AU - Belli, James A.

AU - Frenkel, Eugene P.

N1 - Funding Information: This investigation was supported in part by USPHS Grants CA27967 (Y.C.A.) and CA34269 (J.A.B.) from the National Cancer Research Institute and by the Nasher Family Cancer Research Program (E.P.F.).

PY - 1992/4/15

Y1 - 1992/4/15

N2 - Doxorubicin (DOX, Adriamycin) binds with high affinity to cellular membranes inflicting multiple lesions which are believed to be important in DOX-mediated neoplastic cell death. Using fluorescence and radioactive [14-14C-14]DOX assays for DOX, we have measured the partitioning of DOX between the cytosolic and membrane fractions of erythrocytes and of DOX-sensitive (V-79) and resistant (LZ) Chinese hamster lung fibroblast cells. In both erythrocytes and fibroblasts, a significant fraction of DOX was associated with the membrane fraction. More significantly, the quantity of lipid-bound DOX in the fibroblasts correlated with the cell's susceptibility to DOX. The significance of these findings in the context of existing knowledge about DOX-membrane interactions is discussed.

AB - Doxorubicin (DOX, Adriamycin) binds with high affinity to cellular membranes inflicting multiple lesions which are believed to be important in DOX-mediated neoplastic cell death. Using fluorescence and radioactive [14-14C-14]DOX assays for DOX, we have measured the partitioning of DOX between the cytosolic and membrane fractions of erythrocytes and of DOX-sensitive (V-79) and resistant (LZ) Chinese hamster lung fibroblast cells. In both erythrocytes and fibroblasts, a significant fraction of DOX was associated with the membrane fraction. More significantly, the quantity of lipid-bound DOX in the fibroblasts correlated with the cell's susceptibility to DOX. The significance of these findings in the context of existing knowledge about DOX-membrane interactions is discussed.

KW - Adriamycin

KW - Chinese hamster lung

KW - V-79 and LZ

KW - [14-C]doxorubicin

KW - anthracycline

KW - doxorubicin

KW - drug resistance

KW - fibroblast cell lines

KW - subcellular partitioning of DOX

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DO - 10.1016/0304-3835(92)90060-9

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AN - SCOPUS:0026506407

SN - 0304-3835

VL - 63

SP - 109

EP - 116

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

The relationship of doxorubicin binding to membrane lipids with drug resistance

Abstract

Keywords

ASJC Scopus subject areas

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