Uptake, efflux, and hydrolysis of aclacinomycin A in Friend leukemia cells.
The kinetics of uptake by cells and nuclear incorporation of aclacinomycin A was studied in Friend leukemia cells. It was shown that uptake is a very rapid process. The intracellular concentration is maximum in 10 min and mainly (about 75%) localized in the nucleus. Most of the incorporated drug will disappear from the cell by a two-step mechanism: (a) efflux from the nucleus to the cytoplasm; and (b) deglycosidation at C-7 to the alkavinone form in the cytoplasmic fraction. The cellular uptake was temperature dependent but was not prevented by sodium azide treatment. We assumed, therefore, that it is related to the composition and to the dynamic structure of the cell surface membrane. Nuclear outward transport and deglycosidation were inhibited by sodium azide and low temperatures; this suggests that they are regulated by an active transport process and by an enzymatic activity, respectively.
D015250:Aclarubicin; D000818:Animals; D001386:Azides / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005622:Friend murine leukemia virus; D007942:Leukemia, Experimental / Q000378:metabolism*; D009279:Naphthacenes / Q000494:pharmacology; D013696:Temperature; D014412:Tumor Virus Infections / Q000378:metabolism*
D001386:Azides; D009279:Naphthacenes; D015250:Aclarubicin