Cholesterol based antineoplastic strategies.
Manipulation of cholesterol metabolism open several possibilities of interfering with the growth of malignant cells. Deprivation of cholesterol decreases the velocity of growth and alters the composition of the cell membrane. The high requirement for LDL of malignant cells can be utilized for drug targeting. Proliferation assays were performed with neuroblastoma cells and cell lines of acute myeloid leukemia deprived of cholesterol by inhibition of HMG-CoA-reductase or culture in LDL-deficient medium. The cholesterol content of the cell membrane when reduced to 50% had no effect on the toxicity of LAK-cells but the toxicity of the fluorescent dye merocyanine MC 540 was enhanced two-fold. LDL-mediated drug targeting to AML cells was performed with oxidized LDL and showed toxic reactions. These results proved that cholesterol deprivation could be used to support some therapeutic approaches.
Lenz
M
M
Department of Pediatric Surgery, University of Tübingen, Germany.
Miehe
W P
WP
Vahrenwald
F
F
Bruchelt
G
G
Schweizer
P
P
Girgert
R
R
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D000924:Anticholesteremic Agents; D000970:Antineoplastic Agents; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D008148:Lovastatin