Abstract
Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits nuclear factor-kappa B (NF-kappa B) DNA binding activity. In this report, we investigated the effect of helenalin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Helenalin by itself markedly induced HL-60 cell differentiation in a concentration-dependent manner. Cytofluorometric analysis and cell morphologic studies indicated that helenalin induced cell differentiation predominantly into granulocytes. Protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by helenalin, while p38 mitogen-activated protein kinase (MAPK) inhibitors did not. Moreover, helenalin enhanced PKC activity and protein level of PKC beta I and PKC beta II isoforms, and also increased the level of pERK in a concentration-dependent manner. In addition, the enhanced levels of cell differentiation closely correlated with the decreased levels of NF-kappa B binding activity by helenalin. These results indicate that PKC, ERK, and NF-kappa B may be involved in HL-60 cell differentiation induced by helenalin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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Alkaloids
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Androstadienes / pharmacology
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Antineoplastic Agents, Phytogenic / pharmacology
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Benzophenanthridines
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Cell Differentiation / drug effects*
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Cell Proliferation / drug effects
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Chromones / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Flavonoids / pharmacology
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HL-60 Cells
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Humans
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Indoles / pharmacology
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Lactones / pharmacology
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Maleimides / pharmacology
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Models, Biological
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Morpholines / pharmacology
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Phenanthridines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Sesquiterpenes / pharmacology*
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Sesquiterpenes, Guaiane
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Signal Transduction / drug effects
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Wortmannin
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Alkaloids
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Androstadienes
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Antineoplastic Agents, Phytogenic
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Benzophenanthridines
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Indoles
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Lactones
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Maleimides
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Morpholines
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NF-kappa B
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Phenanthridines
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Phosphoinositide-3 Kinase Inhibitors
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Sesquiterpenes
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Sesquiterpenes, Guaiane
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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helenalin
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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chelerythrine
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Protein Kinase C
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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bisindolylmaleimide I
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Wortmannin