Abstract | BACKGROUND: METHODS: AML blasts derived from two cell lines (HL-60 and AML-2) were incubated with increasing concentrations of either simvastatin alone or simvastatin alone for 24 hours with ARA-C added thereafter. The effect of the drugs on cell proliferation in liquid culture (3H thymidine uptake) and on clonogenic assay was analyzed. RESULTS: We found that the number of proliferating AML blasts ( suspension cultures) and colony formations ( agar cultures) of both cell lines declined significantly after incubation with simvastatin. Preincubation of both cell lines with simvastatin by the addition of increasing concentrations of ARA-C produced a degree of growth inhibition that was significantly greater than that of the individual compounds. This antigrowth interaction was additive rather than synergistic. CONCLUSIONS: We conclude that simvastatin has a major antiproliferative effect on AML blasts in vitro. Also, the combination of simvastatin and ARA-C significantly enhanced the antiproliferative effect of each drug. These findings may open new avenues in both the laboratory and clinical research of the treatment of leukemia.
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Authors | M Lishner, A Bar-Sef, A Elis, I Fabian |
Journal | Journal of investigative medicine : the official publication of the American Federation for Clinical Research
(J Investig Med)
Vol. 49
Issue 4
Pg. 319-24
(Jul 2001)
ISSN: 1081-5589 [Print] England |
PMID | 11478407
(Publication Type: Journal Article)
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Chemical References |
- Anticholesteremic Agents
- Antimetabolites, Antineoplastic
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Cytarabine
- Simvastatin
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Topics |
- Anticholesteremic Agents
(administration & dosage)
- Antimetabolites, Antineoplastic
(administration & dosage)
- Cell Division
(drug effects)
- Cytarabine
(administration & dosage)
- Drug Synergism
- HL-60 Cells
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(administration & dosage)
- Leukemia, Myeloid, Acute
(drug therapy, pathology)
- Simvastatin
(administration & dosage)
- Tumor Cells, Cultured
- Tumor Stem Cell Assay
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