Analysis of intracellular retention of morpholinyl anthracyclines in multidrug resistant cancer cells by interactive laser cytometry

Derick H Lau, G. E. Duran, B. I. Sikic

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Interactive laser cytometry was applied to measure intracellular fluorescence of doxorubicin (DOX) accumulation in a uterine sarcoma cell line, MES-SA and a series of multidrug resistant sublines, Dx0.3, Dx1 and Dx5. Exposure of each cell line to 10 μM DOX for 2 h resulted in an intracellular fluorescent level directly correlated to its sensitivity to the drug but inversely related to its cellular P-glycoprotein (P-gp) level. The morpholinyl anthracyclines, methoxymorpholinyl DOX (MMDX) and morpholinyl DOX (MRA), were equally highly cytotoxic against the multidrug sensitive and resistant cancer cells. After exposure to 10 μM of MMDX or MRA for 2 h, the multidrug resistant cells, Dx5, retained as much intracellular fluorescence as the multidrug sensitive cells, MES-SA. In the resistant cells, the intracellular fluorescence of MMDX or MRA was 8 fold higher than that of DOX. Interactive laser-cytometer is a useful tool for screening cancer cells with the MDR phenotype and for identifying new anthracyclines effective against drug resistant malignancies.

Original languageEnglish (US)
Pages (from-to)1273-1277
Number of pages5
JournalInternational Journal of Oncology
Volume5
Issue number6
StatePublished - 1994

Keywords

  • laser cytometry
  • morpholinyl anthracyclines
  • multidrug resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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