Influence of serum levels on leukemic cell destruction by the ether lipid ET-18-OCH3.
The effect of serum on the antineoplastic action of the alkyl-lysophospholipid 1-octadecyl-2-O-methyl-sn-glycerol-3-phosphocholine (ET-18-OCH3) was studied in two human leukemia cell lines, HL60 and K562, and in leukemic cells of patients. Decreasing amounts of serum in the culture medium enhanced the cytotoxic action of ET-18-OCH3 dramatically in both cell lines and in the leukemic cells, as measured by cell survival and proliferation. Uptake of ET-18-OCH3 was likewise increased at reduced serum levels. Similar effects were obtained when fetal calf serum (FCS) in the culture medium was substituted by bovine serum albumin (BSA, fatty acid free). Selectivity of the alkyl-lysophospholipid at reduced serum or BSA level was demonstrated by clonogenic assays of normal marrow progenitor cells. Our study provides an optimalization of the purging conditions in autologous bone marrow transplantation, by using a low concentration of BSA during ET-18-OCH3 treatment (20 micrograms/ml for 4 h) in serum-free culture medium.
Heesbeen
E C
EC
Department of Hematology, University Hospital Utrecht, The Netherlands.
Rijksen
G
G
van Heugten
H G
HG
Verdonck
L F
LF
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001685:Biological Factors / Q000097:blood* / Q000494:pharmacology*; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000097:blood; D010742:Phospholipid Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D001685:Biological Factors; D016895:Culture Media, Serum-Free; D010742:Phospholipid Ethers; C026659:edelfosine; D012710:Serum Albumin, Bovine