Monocytic differentiation of HL60 cells induced by potent analogs of vitamin D3 precedes the G1/G0 phase cell cycle block

F. Zhang, J. J. Godyn, M. Uskokovic, L. Binderup, G. P. Studzinski

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31 Scopus citations


Abstract. Differentiation of mammalian cells is accompanied by reduced rates of proliferation and an exit from the cell cycle. Human leukemic cells HL60 present a widely used model of neoplastic cell differentiation, and acquire the monocytic phenotype when exposed to analogs of vitamin D3 (VD3). The maturation process is accompanied by two blocks in the cell cycle: an arrest in the G1/G0 phase, and a recently described G2+ 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 compound with its potency as a differentiation‐inducing agent. We found that in general there was a good correlation between the effects of these compounds on the cell cycle and on differentiation, but the best cell cycle predictor of differentiation potency was the extent of accumulation of the cells in the G2 compartment. All analogs induced a marked decrease in the mitotic index, and polynucleation of HL60 cells was produced, especially by compounds which were effective as inducers of differentiation. Time course studies showed that induction of differentiation was accompanied by a transient increase of the proportion of cells in the G2+ M compartment, but preceded the G1 to S, and the G2 compartment blocks. These studies indicate that complex changes in the cell cycle traverse accompany, but do not precede, the acquisition of the monocytic phenotype by HL60 cells.

Original languageEnglish (US)
Pages (from-to)643-654
Number of pages12
JournalCell Proliferation
Issue number11
StatePublished - Nov 1994

All Science Journal Classification (ASJC) codes

  • Cell Biology


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