Toxic reactions of oxidized LDL on cells of acute myeloid leukemia.
In AML patients LDL concentration of the serum is reduced due to the high LDL receptor activity of the AML cells. This phenomenon enables the use of LDL particles as vehicles for drug targeting. Toxic lipid peroxides and aldehydes were introduced into LDL particles by the simple but effective oxidation with 10 microM CuSO4. Up to 250 nmol peroxides and 6 nmol malondialdehyde were formed per mg LDL protein within 30 h of oxidation. This oxidized LDL is effectively taken up by AML cells of the FAB type M3 and M5 indicating the presence of scavenger receptors on these cells. Within 96 h 61-84% of the AML cells are killed by the oxidized LDL. Our results open a possibility to achieve specificity for targeting lipophilic antineoplastic drugs towards AML cells using oxidized LDL as vehicles. The use of oxidized LDL as drug carrier is recommended for purging of AML bone marrow because hematopoietic stem cells that don't possess scavenger receptors are protected from toxic action.
Vahrenwald
F
F
Department of Pediatric Surgery, Klinikum Schnarrenberg, University of Tübingen, Germany.
Galka
K
K
Jürgens
G
G
Bruchelt
G
G
Girgert
R
R
Schweizer
P
P
D019327:Copper Sulfate / Q000737:chemistry; D004492:Edetic Acid / Q000737:chemistry; D004586:Electrophoresis; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008054:Lipid Peroxides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D004492:Edetic Acid; D019327:Copper Sulfate