Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells.
The vitamin D3 derived hormone 1.25 (OH)2 vitamin D3 (1,25 D3) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1.25 D3 reduced proliferation as measured by 3H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 4.8 nM. The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4. The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33. When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia.
Frankenberger
M
M
Institute of Immunology, University of München, Germany.
Hofmann
B
B
Emmerich
B
B
Nerl
C
C
Schwendener
R A
RA
Ziegler-Heitbrock
H W
HW
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D053493:Cholestanetriol 26-Monooxygenase; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells / Q000473:pathology; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D008081:Liposomes; D013250:Steroid Hydroxylases / Q000008:administration & dosage / Q000494:pharmacology*
D008081:Liposomes; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase