Effect of 5-aza-2'-deoxycytidine and vitamin D3 analogs on growth and differentiation of human myeloid leukemic cells.
OBJECTIVE
The object of this study was to investigate the antineoplastic action of 5-aza-2'-deoxycytidine (5-AZA) in combination with vitamin D analogs on HL-60 and NB-4 myeloid leukemic cells. The vitamin D analogs chosen for this investigation were 1,25-(OH)2-23-yne-cholecalciferol (23-D) and 1,25-(OH)2-delta16-23-yne-cholecalciferol (16-23-D) since they have the potential to be used clinically owing to their minimal action on calcium metabolism.


METHODS
HL-60 and NB-4 leukemic cells were incubated with different concentrations of 5-AZA and either 23-D or 16-23-D and their antineoplastic action determined by inhibition of DNA synthesis and growth, induction of differentiation and colony assay.


RESULTS
5-AZA in combination with either vitamin D analog produced a greater growth inhibition and induction of differentiation than either agent alone. For HL-60 leukemic cells the combination of 5-AZA with either analog produced a synergistic loss of clonogenicity. These effects on clonogenicity correlated with the effects of the combination on inhibition of growth and DNA synthesis.


CONCLUSIONS
These results suggest that vitamin D analogs may enhance the antileukemic action of 5-AZA and that it may be interesting to test these agents in combination in patients with myeloid leukemia.
Doré
B T
BT
Département de pharmacologie, Université de Montréal, Québec, Canada.
Chomienne
C
C
Momparler
R L
RL
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D002762:Cholecalciferol; D000077209:Decitabine; D001374:Azacitidine