In vitro cytotoxicity of the LDE: daunorubicin complex in acute myelogenous leukemia blast cells.
Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL receptors. LDE is a lipid microemulsion easily synthesized in vitro which is known to mimic the metabolic pathway of LDL. We used LDE as a carrier for daunorubicin and assayed the cytotoxicity of the complex using AML blast cells since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The LDE:daunorubicin complex killed 46.7% of blast cells and 20.2% of normal bone marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and protecting normal tissues.
Dorlhiac-Llacer
P E
PE
Departamento de Hematologia e Hemoterapia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil. llacer.ops@zaz.com.br
Marquezini
M V
MV
Toffoletto
O
O
Carneiro
R C
RC
Maranhão
R C
RC
Chamone
D A
DA
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D002648:Child; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004338:Drug Combinations; D004655:Emulsions; D005260:Female; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D011973:Receptors, LDL / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014410:Tumor Stem Cell Assay
D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D004655:Emulsions; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D003630:Daunorubicin