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KMID : 1134819980270010141
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Journal of the Korean Society of Food Science and Nutrition
1998 Volume.27 No. 1 p.141 ~ p.148
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Anticancer Effects of Vitamin D₃ Analog on Human Leukemic Cell Line(U937) and Role of Vitamin D₃ Analog on Immune Function of Human Peripheral Blood Lymphocytes
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Jung Soo-Ja
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Abstract
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This study describes the effects of 1,25-dihydroxyvitamin D₃[1,25(OH)₂D₃, calcitriol] analog, 1,25(OH)₂-16ene-23yne-D₃ on proliferation and differentiation of the human histiocytic lymphoma cell line U937. This paper also describes the effects of 1,25(OH)₃-l6ene-23yne-D₃ on γ-interferon(IFN-γ) synthesis by phytohemagglutinin-activated peripheral blood lymphocytes(PBLs). In the present investigation, 1,25(OH)₂-l6ene-23yne-D₃ was compared to the natural metabolite of vitamin D₃, 1,25 (OH)₂D₃. 1,25(OH)₂-l6ene-23yne-D₃ was more potent than 1,25(OH)₂D₃ for inhibition of proliferation and induction of differentiation of U937 cells. Its effects on inhibition of proliferation was about 30- fold more potent than 1,25(OH)₂D₃. On induction of differentiation as measured by nonspecific esterase (NSE) activity and morphologic change, this analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability of surface. After 3 days in culture, a more significant supression of IFN-γ synthesis by PBLs was achieved with 1,25(OH)₂-l6ene-23yne-D₃ than with 1,25(OH)₂D₃. The effects of this analog on supression of IFN-γ synthesis was a dose-dependent manner, with peak activity at 10^(-7)M. The strong direct effects of 1,25(OH)₂-l6ene-23yne-D₃ on cell proliferation and cell differentiation, make this compound an interesting candidate for clinical studies for several types of malignancies, and the effects on supression of IFN-γ synthesis provide the further evidence for a role of 1,25(OH)₂-16ene-23yne-D₃ in immunoregulation.
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KEYWORD
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1,25(OH)2-16ene-23yne-D3, U937 leukemia cell differentiation, IFN-${\gamma}$ synthesis
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