F. Zhang et al., MONOCYTIC DIFFERENTIATION OF HL-60 CELLS INDUCED BY POTENT ANALOGS OFVITAMIN-D-3 PRECEDES THE G(1) G(0)-PHASE CELL-CYCLE BLOCK/, Cell proliferation, 27(11), 1994, pp. 643-654
Differentiation of mammalian cells is accompanied by reduced rates of
proliferation and an exit from the cell cycle. Human leukemic cells HL
60 present a widely used model of neoplastic cell differentiation, and
acquire the monocytic phenotype when exposed to analogs of vitamin D-
3 (VD3). The maturation process is accompanied by two blocks in the ce
ll cycle: an arrest in the G(1)/G(0) phase, and a recently described G
(2) + M block. In this study we have analyzed the traverse of the cell
cycle phases of the well-differentiating HL60-G cells exposed to one
of ten analogs of VD3, and compared the cell cycle effects of each com
pound with its potency as a differentiation-inducing agent. We found t
hat in general there was a good correlation between the effects of the
se compounds on the cell cycle and on differentiation, but the best ce
ll cycle predictor of differentiation potency was the extent of accumu
lation of the cells in the G(2) compartment. All analogs induced a mar
ked decrease in the mitotic index, and polynucleation of HL60 cells wa
s produced, especially by compounds which were effective as inducers o
f differentiation. Time course studies showed that induction of differ
entiation was accompanied by a transient increase of the proportion of
cells in the G(2) + M compartment, but preceded the G(1) to S, and th
e G(2) compartment blocks. These studies indicate that complex changes
in the cell cycle traverse accompany, but do not precede, the acquisi
tion of the monocytic phenotype by HL60 cells.