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Increased Sensitivity of Myeloid Leukemia Cell Lines: Potential of Lovastatin as Bone-Marrow-Purging Agent.
- Source :
-
Acta Haematologica . 2000, Vol. 104 Issue 2/3, p72-79. 8p. - Publication Year :
- 2000
-
Abstract
- Lovastatin reduces the isoprenylation of p21[sup ras] via suppression of mevalonic acid generation. Lovastatin has been shown to reduce tumor cell proliferation in a dose-dependent manner. Here, the potential of lovastatin for purging leukemia cells from bone marrow was investigated using the myeloblastic cell lines K562 and KG-1 as a model system, derived from an erythroleukemia and an acute myelogenous leukemia, respectively. Optimal purging conditions were determined using an MTT proliferation and a leukemia colony assay. Elimination of leukemia cells was time- and dose-dependent. Depletion of K562 was 2.5 logs for 100 μM of lovastatin at 72 h of incubation. Compared to another purging agent, 100 μg/ml mafosfamide had an activity comparable to 100 mM lovastatin. Interestingly, KG-1 acute myelogenous leukemia cells were even more sensitive to lovastatin than K562 cells. In clonogenic assays, 100 μM of lovastatin resulted in a 3- to 4-log reduction of K562 colonies. Lovastatin had a progressive effect on normal hematopoietic progenitor cells. At a concentration of 100 μM of lovastatin, CFU-GM colonies were reduced by 1–2 logs. In conclusion, a differential effect on leukemia and normal progenitor cells could be detected in a clonogenic assay. These results suggest that lovastatin deserves further study as an agent for ex vivo marrow purging.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Subjects :
- *BONE marrow transplantation
*MYELOID leukemia
*CANCER cells
*ENZYMES
Subjects
Details
- Language :
- English
- ISSN :
- 00015792
- Volume :
- 104
- Issue :
- 2/3
- Database :
- Academic Search Index
- Journal :
- Acta Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 11333605
- Full Text :
- https://doi.org/10.1159/000039755