Effect of gamma-linolenic acid on cellular uptake of structurally related anthracyclines in human drug sensitive and multidrug resistant bladder and breast cancer cell lines

This study investigated the effect on drug uptake in multidrug resistant ce lls by the incorporation of the essential fatty acid gamma-linolenic acid ( GLA). The cell lines used were the MCF-7/R resistant human breast: cancer a nd MGH-U1/R bladder cancer. Uptake of drugs (doxorubicin, epirubicin, mitox antrone and idarubicin) after the incorporation of GLA was investigated qua ntitatively by flow cytometry and qualitatively by confocal microscopy, The re was no observable overall increase in drug uptake due to GLA incorporati on into the cells as shown by flow cytometry. However, an increase in uptak e of the chemotherapeutic agent idarubicin was observed in GLA-treated resi stant cells compared with untreated cells using the confocal microscope. Th is overall increase in cellular drug uptake was not accompanied by a change in cellular drug distribution. Only one drug, mitoxantrone, displayed a ch ange in intracellular drug distribution due to GLA incorporation into MCF-7 /R cells. This suggests that essential fatty acid incorporation into the ce llular membranes of some resistant cells may cause a shift in the intracell ular distribution of certain chemotherapeutic drugs. (C) 1999 Elsevier Scie nce Ltd. All rights reserved.