FLOW CYTOMETRIC MONITORING OF ANTHRACYCLINE ACCUMULATION AFTER ANTINEOPLASTIC ETHER PHOSPHOLIPID TREATMENT

Ether phospholipids are new anti-neoplastic drugs that have been found active against a variety of tumor cell lines, including drug-resistan t sublines. We have characterized the antiproliferative activity of th ree ether phospholipids, i.e. ET-18-OCH3 (Edelfosine), BM 41.440 (llmo fosine) and a new aza-derivative (BN 52205), on three leukemic cell li nes, i.e. K562 (chronic myeloid leukemia, blast crisis), HL60 (promyel ocytic acute leukemia) and CEM (T cell leukemia), and their respective drug-resistant sublines, i.e. K562-ADR (adryamicin resistant), HL60-D NR [daunorubicin (DNR) resistant] and CEM-VLB (vinblastin resistant). These resistant sublines have been found to express the multidrug-resi stant phenotype, revealed by the presence of the P-glycoprotein (PgP) using different monoclonal antibodies. Increased cellular accumulation of the fluorescent anthracycline has been found in both sensitive and resistant cell lines after different ether phospholipid treatment tim es. In resistant cells, the ether phospholipid effect on DNR accumulat ion has also been found after blocking the PgP function by verapamil a nd cyclosporin A. These results confirm that the ether phospholipid ac tion is closely linked with the membrane biochemical composition and t hat these new anti-tumor drugs are able to change the dynamic structur al organization of the tumor cell membrane.