Cellular daunomycin fluorescence in multidrug resistant 2780AD cells and its relation to cellular drug localisation.
Multidrug resistant (MDR) 2780AD human ovarian carcinoma cells were loaded with the fluorescent anticancer agent daunomycin (DN). Fluorescence anisotropy was lower than for corresponding A2780 wild-type cells, indicating that DN was less rigidly bound than in the wild-type cells. Average fluorescence quenching of DN was lower for 2780AD cells. Data were fitted into a model with a highly quenched fraction (fraction A), corresponding to DN intercalated in DNA, and an unquenched fraction (fraction B). The ratio A/B was one order of magnitude lower for the MDR cells than for the wild-type cells. Two other MDR cell lines were investigated and low A/B ratios were found in both cases. Thus, evidence has been provided that in MDR cells the DNA-bound fraction is relatively low and that more free DN is present, for example in acidic vesicles.
Lankelma
J
J
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Mülder
H S
HS
van Mourik
F
F
Wong Fong Sang
H W
HW
Kraayenhof
R
R
van Grondelle
R
R
D004273:DNA, Neoplasm / Q000378:metabolism*; D003630:Daunorubicin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005454:Fluorescence Polarization; D006801:Humans; D007364:Intercalating Agents; D008954:Models, Biological; D010051:Ovarian Neoplasms; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007364:Intercalating Agents; D003630:Daunorubicin