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Effects of transforming growth factor-beta and activin A on vitamin D3-induced monocytic differentiation of myeloid leukemia cells.

We examined the effects of transforming growth factors beta(TGF-beta) alone and in combination with 1 alpha,25-dihydroxyvitamin D3 (VD3) on human leukemic cell lines (HEL/S, HL-60 and K562). TGF-beta 1 alone at higher concentrations induced monocytic differentiation of HEL/S cells. Combinations of TGF-beta 1 and VD3 synergistically inhibited cell proliferation and induced monocytic differentiation of HEL/S and HL-60 cells. TGF-beta 2 (a subtype of TGF-beta) and erythroid differentiation factor (EDF/Activin A, a member of the TGF-beta gene family) also inhibited growth and induced monocytic differentiation of HL-60 cells in synergy with VD3. Thus combinations of VD3 and TGF-beta (TGF-beta 1, -beta 2, or EDF) acted synergistically in inhibiting cell proliferation and inducing monocytic differentiation of human leukemia cells.