Potentiation of 1,25-dihydroxyvitamin D(3)-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide,a germacranolide sesquiterpene lactone |
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Authors: | Kim Seung H Kang So N Kim Hyeoung J Kim Tae S |
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Affiliation: | Immunology Laboratory, College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, South Korea. |
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Abstract: | Costunolide, a germacranolide sesquiterpene lactone that exists in several medicinal plants, is known to be a possible anti-cancer and chemopreventive agent for tumorigenesis. In this report, we investigated the effect of costunolide on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5nM 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). Costunolide by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that costunolide potentiated 1,25-(OH)(2)D(3)-induced cell differentiation predominantly into monocytes. Inhibitors for PKC, PI3-K, and ERK markedly inhibited HL-60 cell differentiation induced by costunolide in combination with 1,25-(OH)(2)D(3). In addition, pretreatment of HL-60 cells with costunolide before the 1,25-(OH)(2)D(3) addition also potentiated cell differentiation in a concentration- and time-dependent manner, and the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-kappaB-binding activity by costunolide. These results indicate that PKC, PI3-K, ERK and NF-kappaB may be involved in 1,25-(OH)(2)D(3)-mediated cell differentiation enhanced by costunolide. |
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Keywords: | EMSA, electrophoretic mobility shift assay ERK, extracellular signal-regulated kinase MAPK, mitogen-activated protein kinase NBT, nitroblue tetrazolium NF-κB, nuclear factor-kappaB 1,25-(OH)2D3, 1,25-dihydroxyvitamin D3 PI3-K, phosphatidylinositol 3-kinase PKC, protein kinase C. |
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