Selective inhibition of primary acute myeloid leukaemia cell growth by simvastatin.
Primary human acute myeloid leukaemic (AML) cells from bone marrow (BM) and peripheral (PB), the human myeloblastic leukaemia cell line (HL60) and normal human BM mononuclear cells were cultured in serum-free medium. The survival of progenitor cells from normal BM, HL60 and AML cell populations was reduced over a range of concentrations of simvastatin. This dose response relationship was more pronounced in HL60 and AML cell cultures, indicating greater sensitivity of AML progenitor cells compared with normal BM progenitors. Short-term exposure (18 h) to a range of concentrations of simvastatin showed the same differential response between leukaemic and normal BM cells in terms of clonogenicity. At a concentration of 10 micrograms/ml progenitor cell survival remained above 65% for normal BM while at this concentration leukaemia progenitor cell survival fell below 25% of the untreated values. The differential effect of simvastatin on normal and leukaemic progenitor cells may have value in the clinical management of AML. The possible use of simvastatin, or related drugs, as adjuvants to conventional chemotherapy including in vitro BM purging, merits consideration.
Newman
A
A
Section of Medicine, Institute of Cancer Research, Sutton, Surrey, UK.
Clutterbuck
R D
RD
Powles
R L
RL
Millar
J L
JL
D000208:Acute Disease; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D002999:Clone Cells; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000166:cytology; D019821:Simvastatin; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin