Abstract
Rutaecarpine is a quinazolinocarboline alkaloid isolated from a traditional Chinese medicinal fruit, Evodia rutaecarpa. In the present study, we investigated the effect of rutaecarpine on CYP1A1 expression mediated by [Ca(2+)] and the AhR pathway in mouse hepatoma Hepa-1c1c7 cells. Rutaecarpine also significantly increased CYP1A1 enzyme activity and mRNA and protein levels. Rutaecarpine markedly induced XRE and AhR binding activity. CH-223191, an AhR antagonist, blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression. In addition, rutaecarpine remarkably induced the phosphorylation of Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK). W7 and BAPTA/AM, a CaM antagonist and an intracellular Ca(2+) chelator, respectively, blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression. These results indicate that rutaecarpine induces CYP1A1 expression through AhR- and calcium-dependent mechanisms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Azo Compounds / pharmacology
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Basic Helix-Loop-Helix Transcription Factors
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Binding Sites
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Calcium / metabolism*
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line, Tumor
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Chelating Agents / pharmacology
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Cytochrome P-450 CYP1A1 / biosynthesis*
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Cytochrome P-450 CYP1A1 / genetics
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal / pharmacology*
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Enzyme Induction
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Indole Alkaloids / pharmacology*
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Liver / drug effects*
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Liver / enzymology
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Mice
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Phosphorylation
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Promoter Regions, Genetic / drug effects
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Protein Kinase Inhibitors / pharmacology
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Pyrazoles / pharmacology
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Quinazolines / pharmacology*
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RNA, Messenger / metabolism
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Receptors, Aryl Hydrocarbon / agonists*
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Receptors, Aryl Hydrocarbon / antagonists & inhibitors
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Receptors, Aryl Hydrocarbon / metabolism
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Sulfonamides / pharmacology
Substances
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2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide
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Ahr protein, mouse
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Azo Compounds
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Basic Helix-Loop-Helix Transcription Factors
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Chelating Agents
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Drugs, Chinese Herbal
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Indole Alkaloids
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Protein Kinase Inhibitors
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Pyrazoles
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Quinazolines
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RNA, Messenger
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Receptors, Aryl Hydrocarbon
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Sulfonamides
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Egtazic Acid
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W 7
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rutecarpine
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Cytochrome P-450 CYP1A1
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Calcium-Calmodulin-Dependent Protein Kinases
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Calcium