1Department of Internal Medicine, College of Medicine, Chung-Ang University. 2Department of Internal Medicine, Hanyang University School of Medicine. 3Cancer Research Center, Seoul National University College of Medicine, Seoul, Korea. 4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
ABSTRACT
PURPOSE: Vitamin D3 was shown to arrest the growth of acute myelogenous leukemic cells and transforming growth factor- B1 (TGF- B1) was reported to be involved in the mechanism of vitamin D3. We studied the growth inhibitory effect of 1,25(OH)2-vitamin D3(C) and its analogue (EB1089) in leukemic cell lines and the changes in the secretion or the activation of TGF-B1 in the supernatant and the status of TGF-B1 type II receptor.
MATERIALS AND METHODS: Growth inhibition by vitamin D3 and TGF-B1 in 5 leukemic cell lines (HEL, HL-60, U937, KG-1, K562) were assessed with clonogenic and [3H]thymidine assay respectively. TGF-B type II receptor status was examined by Southern and Northern blotting. The concentrations of TGF- B1 in the supernatant were quantitated by enzyme immunoassay.
RESULTS: The growth of HEL, HL-60, U937 were inhibited in a dose-dependent fashion by both C and EB1089, more markedly by the latter. Anti-TGF-B neutralizing antibody partially reversed the growth inhibition. TGF-B1 markedly inhibited the growth of HEL, U937, KG-1, SNU-16 dose dependently while HL-60 and K562 showed no growth inhibition. HEL secreted latent TGF- 1 and HL-60 activated latent TGF- B1 or secreted active TGF-B1 irrespective of the treatment with vitamin D3. In U937, vitamin D3 increased the concentration of both active and latent TGF-B1. Deletion or abnormal expression of TGF- B type II receptor gene was not found in the 5 cell lines examined.
CONCLUSION: Vitamin D3 has various pattern of growth inhibition in acute myelogenous leukemia and inhibits the growth of some cell lines by secretion or activation of TGF-B1. Abnormality of TGF-B type II receptor DNA or mRNA seems to be rare.
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