J Korean Cancer Assoc.  1998 Aug;30(4):827-841.

Study on Growth Suppression Effect of Vetamin D3 Mediated by Transfrorming Growth Factor-B1(TGF-B1) in Acute Myelogenous Leukemic Cell

• Jung CW
• Lee SJ
• Ahn MJ
• Jung TJ
• Kim IS
• Choi IY
• Seol JK
• Kim ES
• Kim BK
• Lee YY

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.

Keyword

Vitamin D; EB1089; Acute myelogenous leukemia; TGF-B1

MeSH Terms

Antibodies, Neutralizing
Blotting, Northern
Cell Line
Cholecalciferol
DNA
Immunoenzyme Techniques
Leukemia, Myeloid, Acute
RNA, Messenger
Vitamin D
Antibodies, Neutralizing
Cholecalciferol
DNA
RNA, Messenger
Vitamin D