The physiologically active form of vitamin D-3, 1,25-dihydroxy-vitamin
D-3 (1,25(OH)(2)D-3), induces differentiation of several types of mye
loid leukaemia cells. The acquisition of monocyte-like phenotype is ac
companied by slower progression through the cell cycle, and G(1) block
has been reported to be the basis of this effect. It is shown here th
at human promyelocytic leukaemia HL60 cells treated with analogues of
vitamin D-3 which are potent inducers of monocytic differentiation hav
e an additional cell cycle block. Exposure to 10(-7)M 1,25(OH)(2)D-3 o
r 1,25-(OH)(2)-16-ene-D-3 resulted in monocytic differentiation and th
e expected G(1) block evident at approximately 48 h in a rapidly diffe
rentiating variant of HL60 cells (HL60-G), and at 96 h in the more slo
wly differentiating HL60-240 cells. In addition, a G(2)+M block was no
ted at approximately 72 h in HL60-G and HL60-240 cells. Exposure to vi
tamin D-3 analogues also markedly increased the number of dikaryons, s
uggesting that cytokinesis was impaired more than karyokinesis. Treatm
ent with a third analogue 25-hydroxy-16,23-diene-D-3 produced little d
ifferentiation and had minimal effects on the cell cycle parameters. T
hese findings indicate that vitamin D-3 analogues regulate cell prolif
eration by control of the transition of G(1) and G(2)+M phases, remini
scent of the cdc2/CDK2 type of cell cycle control.