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 cells 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 and MGH-U1/R bladder cancer. Uptake of drug (doxorubicin, epirubicin, mitoxantrone and idarubicin) after the incorporation of GLA was investigated quantitatively by flow cytometry and qualitatively by confocal microscopy. There was no observable overall increase in drug uptake due to GLA incorporation into the cells as shown by flow cytometry. However, an increase in uptake of the chemotherapeutic agent idarubicin was observed in GLA-treated resistant cells compared with untreated cells using the confocal microscope. This overall increase in cellular drug uptake was not accompanied by a change in cellular drug distribution. Only one drug, mitoxantrone, displayed a change in intracellular drug distribution due to GLA incorporation into MCF-7/R cells. This suggests that essential fatty acid incorporation into the cellular membranes of some resistant cells may cause a shift in the intracellular distribution of certain chemotherapeutic drugs.
Davies
C L
CL
Department of Surgery, Royal Free and University College Medical School, London, U.K.
Loizidou
M
M
Cooper
A J
AJ
Taylor
I
I
D018943:Anthracyclines / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D018943:Anthracyclines; D017965:gamma-Linolenic Acid