The relationship of doxorubicin binding to membrane lipids with drug resistance.
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.
Awasthi
S
S
University of Texas Southwestern Medical Center, Dallas.
Sharma
R
R
Awasthi
Y C
YC
Belli
J A
JA
Frenkel
E P
EP
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008563:Membrane Lipids / Q000097:blood / Q000378:metabolism*
D008563:Membrane Lipids; D004317:Doxorubicin