Abstract
Histone deacetyrase (HDAC) inhibitors induce growth arrest and differentiation of leukemia cell lines and tumor cells derived from a large variety of human tissues. Here we showed that HDAC inhibitors sodium butyrate, TSA, and valproate regulated the expression of Interleukin-18 (IL-18), a cytokine with antitumor and proinflammatory properties, in human acute myeloid leukemia cell lines U937 and HEL. Sodium butyrate increased expression of IL-18 protein and mRNA and activated 1357bp IL-18 gene promoter construct. IL-18 mRNA level was up-regulated by TSA or valproate, which also activated IL-18 full-length promoter. While sodium butyrate or TSA stimulated the 108-bp IL-18 minimal promoter, valproate failed to activate it, indicating that valproate may use a distinct mechanism from sodium butyrate and TSA to activate IL-18 gene expression.
(c)2002 Elsevier Science (USA).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Northern
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Blotting, Western
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Butyrates / pharmacology
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Cell Line
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Cell Survival / drug effects
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Enzyme Inhibitors / pharmacology*
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Gene Expression / drug effects*
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Growth Inhibitors / pharmacology
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / pharmacology
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Interleukin-18 / genetics
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Interleukin-18 / metabolism*
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Leukemia, Erythroblastic, Acute / drug therapy
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Leukemia, Erythroblastic, Acute / metabolism
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Myeloid Cells / cytology
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Myeloid Cells / drug effects*
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Myeloid Cells / metabolism
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Promoter Regions, Genetic / drug effects
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RNA, Messenger / metabolism
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U937 Cells
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Valproic Acid / pharmacology
Substances
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Butyrates
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Enzyme Inhibitors
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Growth Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Interleukin-18
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RNA, Messenger
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trichostatin A
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Valproic Acid