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DC Moore, DL Carter, AK Bhandal and GP Studzinski
UMDNJ-New Jersey Medical School, Newark.
The physiologically active form of vitamin D, 1,25 dihydroxyvitamin D3
[1,25(OH)2D3], was found to inhibit erythroid differentiation of human
leukemic K562 cells. Differentiation was induced by 1 mumol/L
arabinocytosine (Ara-C), 40 mumol/L tiazofurin, 1 mumol/L aphidicolin, or 1
mumol/L hydroxyurea, and was monitored daily by the appearance of
hemoglobin in an increasing proportion of cells. Pretreatment for 48 hours
with 2.4 x 10(-8) mol/L 1,25(OH)2D3, a concentration that is also optimal
for induction of monocytic differentiation of HL-60 cells, reproducibly
inhibited subsequent induction of erythroid differentiation by all of the
above inducers, and modified the morphologic changes that Ara-C produced in
these cells. The inhibition of hemoglobinization was approximately 50%
irrespective of the degree of differentiation produced by the various
inducers, but growth inhibition associated with exposure to the inducers
was not affected by 1,25(OH)2D3. Similar inhibition of differentiation by
1,25(OH)2D3 was observed in mouse erythroleukemia cells MEL-D1B treated
with 5 mmol/L hexamethylenebisacetamide. The inhibitory effect of
1,25(OH)2D3 on erythroid differentiation of K562 cells was abrogated by
cyclohexamide (20 micrograms/mL), an inhibitor of protein synthesis. The
mRNA for 1,25(OH)2D3 receptor (VDR) was detected in K562 cells, and was
downregulated by a 96-hour exposure to 1,25(OH)2D3 or a 48-hour exposure to
Ara-C. The presence of VDR mRNA suggests a physiologic role for 1,25(OH)2D3
in K562 cells that are precursors of erythroid cells. This role is perhaps
to shift the pathways of differentiation from the erythroid to the
monocytic lineage.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
