| pubmed-article:9224728 | pubmed:abstractText | 1alpha,25-Dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and other vitamin D3 (VD3) analogs enhanced the inhibitory effect of Activin A on murine erythroleukemia (MEL) cell proliferation and differentiation in a dose-dependent manner. 1alpha,25-(OH)2D3 inhibited differentiation more potently than proliferation by one order of magnitude. The VD3 analog study demonstrated either effect of VD3 on MEL cells via vitamin D receptor (VDR), as evidenced from the close relationship with the reported affinities for VDR. The effects of 1alpha,25-(OH)2D3 were preceded by the suppression of ornithine decarboxylase (ODC) activity, a rate-limiting enzyme in polyamine metabolism. Difluoromethylornithine (DFMO), an inhibitor of ODC, inhibited MEL cell proliferation, which was reversed by the simultaneous addition of putrescine, a product of ODC, but did not affect differentiation. 1alpha,25-(OH)2D3 inhibited cell differentiation during the phenotype-expression stage as reflected by the inhibition of beta-globin gene expression, while it inhibited proliferation in the commitment stage. Furthermore, it seems unlikely that the different effects of VD3 on proliferation and differentiation may be a result of upregulation of VDR or nongenomic action. In summary, it was suggested that 1alpha,25-(OH)2D3 inhibited Activin A-induced MEL cell proliferation and differentiation by distinct mechanisms and inhibited the proliferation by inhibiting ODC activity. We demonstrated the presence of 1alpha,25-(OH)2D3 action on leukemic cells at physiological concentration, which was distinct from the pharmacological effect of VD3 reported thus far. | lld:pubmed |
