Abstract
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.
Highlights
Low-density lipoprotein (LDL) is the lipoprotein that carries most of the cholesterol contained in the plasma compartment and is removed from the circulation into cells by specific receptors on the cell surface [1]
LDL degradation is up-regulated in several cancer cell lines [3], probably because of the great demand of lipids for synthesis of new membranes required by cell proliferation in neoplasia
RT-PCR had shown that the expression of rLDL is higher in acute myelogenous leukemia (AML) blast cells than in normal bone marrow cells, compared to ßactin expression (Figure 1A)
Summary
Low-density lipoprotein (LDL) is the lipoprotein that carries most of the cholesterol contained in the plasma compartment and is removed from the circulation into cells by specific receptors on the cell surface [1]. It was demonstrated that LDL could be used as a drug carrier to target neoplastic cells, while avoiding normal tissues and organs [5]. Internalization of LDLcontaining chemotherapeutic agents into neoplastic cells resulting in accumulation of the drug in the cytoplasm was demonstrated in several in vitro studies [6,7,8,9]. Individuals with ovarian and endometrial cancer receiving weekly doses of vincristine complexed with LDL did not show any of the side effects commonly associated with the drug [10]. This result demonstrates that a chemotherapeutic agent encapsulated in LDL
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