Potentiation of adriamycin accumulation and effectiveness in adriamycin-resistant cells by aclacinomycin A

Haim Tapiero, Dominique Boulé, Geneviève Trincal, Alain Fourcade, Theodore Lampidis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Variants of Friend leukemia cells (FLC) selected for resistance to either adriamycin (ADM), daunorubicin (DNR) or aclacinomycin A (ACM) by step-wise exposure to each drug, were found to be cross-resistant to ADM and DNR but not to ACM. In addition, an epithelial cell line isolated from normal monkey kidney (CV-1) was found to be intrinsically resistant to ADM and DNR but not to ACM. In contrast, a human breast carcinoma cell line (MCF-7) was found to be sensitive to all three compounds. In these latter cell lines as well as in the FLC variants, lowered intracellular amounts of ADM and DNR correlated with resistance, but ACM levels were the same in sensitive and resistant cells. When cells with either acquired or intrinsic resistance were treated with ACM in combination with ADM or DNR, significant increases in the intracellular amounts of these latter compounds were found. Increased drug accumulation in resistant cells treated this way was accompanied by increased cytotoxicity. When resistant cells were exposed to ACM in combination with other anthracyclines, similar results were obtained. In comparison, these phenomena were not observed when either one of the sensitive cell types (parental FLC and MCF-7) were treated similarly. Since ADM and DNR resistant cells are sensitive to ACM and their resistance circumvented by ACM, this drug may have important clinical applications when used in combination with other anthracyclines.

Original languageEnglish
Pages (from-to)411-418
Number of pages8
JournalLeukemia Research
Volume12
Issue number5
DOIs
StatePublished - Jan 1 1988

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Aclarubicin
Doxorubicin
Daunorubicin
Leukemia
Anthracyclines
Cell Line
Pharmaceutical Preparations
MCF-7 Cells
Haplorhini
Epithelial Cells
Breast Neoplasms
Kidney

Keywords

  • accumulation
  • aclacinomycin A
  • Anthracycline
  • circumvention
  • resistance

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Potentiation of adriamycin accumulation and effectiveness in adriamycin-resistant cells by aclacinomycin A. / Tapiero, Haim; Boulé, Dominique; Trincal, Geneviève; Fourcade, Alain; Lampidis, Theodore.

In: Leukemia Research, Vol. 12, No. 5, 01.01.1988, p. 411-418.

Research output: Contribution to journalArticle

Tapiero, Haim ; Boulé, Dominique ; Trincal, Geneviève ; Fourcade, Alain ; Lampidis, Theodore. / Potentiation of adriamycin accumulation and effectiveness in adriamycin-resistant cells by aclacinomycin A. In: Leukemia Research. 1988 ; Vol. 12, No. 5. pp. 411-418.
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