PMID: 9444941Jan 28, 1998Paper

Toxic reactions of oxidized LDL on cells of acute myeloid leukemia

Leukemia Research
F VahrenwaldP Schweizer

Abstract

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.

References

Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J W JanssenC R Bartram
Nov 22, 1994·Proceedings of the National Academy of Sciences of the United States of America·G M ChisolmP E DiCorleto
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Mar 1, 1996·Annals of Hematology·J OertelD Huhn
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