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 journalArticle

17 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 languageEnglish (US)
Pages (from-to)109-116
Number of pages8
JournalCancer Letters
Volume63
Issue number2
DOIs
StatePublished - 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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    Awasthi, S., Sharma, R., Awasthi, Y. C., Belli, J. A., & Frenkel, E. P. (1992). The relationship of doxorubicin binding to membrane lipids with drug resistance. Cancer Letters, 63(2), 109-116. https://doi.org/10.1016/0304-3835(92)90060-9