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  • Title: Modulation of cell growth, differentiation, and production of interleukin-3 by 1 alpha,25-dihydroxyvitamin D3 in the murine myelomonocytic leukemia cell line WEHI-3.
    Author: Abe J, Moriya Y, Saito M, Sugawara Y, Suda T, Nishii Y.
    Journal: Cancer Res; 1986 Dec; 46(12 Pt 1):6316-21. PubMed ID: 3490908.
    Abstract:
    The effect of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, on the relation between cell growth and differentiation was examined in a murine myelomonocytic leukemia cell line WEHI-3 which is known to produce high levels of interleukin-3. 1 alpha,25(OH)2D3 markedly inhibited proliferation of WEHI-3 cells in a time- and dose-dependent manner. Flow cytometric analysis of the cell cycle by a double staining method using fluorescein isothiocyanate-conjugated anti-bromodeoxyuridine and propidium iodide revealed that 1 alpha,25(OH2D3 increased the proportion and the number of cells accumulating in the G0-G1 phase and decreased those in the S phase. The phenotype of the surface antigens of the cells was of the T-cell lineage, but the cells became positive in macrophage-associated surface markers (Mac-1 and Ia) after treatment with 1 alpha,25(OH)2D3. The vitamin induced phagocytic activity, appearance of Fc receptors, nitroblue tetrazolium-reducing activity, and nonspecific esterase activity, indicating that the vitamin induces the cells to differentiate into macrophages. Furthermore, 1 alpha,25(OH)2D3 inhibited interleukin-3 production by the cells in a time- and dose-dependent manner. These results suggest that 1 alpha,25(OH)2D3 inhibits proliferation of WEHI-3 cells by blocking transition of the cells from the G0-G1 to the S phase, resulting in induction of the G0-G1-arrested cells to differentiate into macrophages. The relation between the suppression by 1 alpha,25(OH)2D3 of cell growth and interleukin-3 production remains to be elucidated in the future.
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