Abstract
The present study identified a novel mechanism for the effects of sanguinarine in vascular smooth muscle cells (VSMC). Sanguinarine treatment of VSMC resulted in significant growth inhibition as a result of G1-phase cell-cycle arrest mediated by induction of p27KIP1 expression, and resulted in a down-regulation of the expression of cyclins and CDKs in VSMC. Moreover, sanguinarine-induced inhibition of cell growth appeared to be linked to activation of Ras/ERK through p27KIP1-mediated G1-phase cell-cycle arrest. Overall, the unexpected effects of sanguinarine treatment in VSMC provide a theoretical basis for clinical use of therapeutic agents in the treatment of atherosclerosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / pharmacology*
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Atherosclerosis / drug therapy
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Atherosclerosis / enzymology
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Atherosclerosis / pathology
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Benzophenanthridines / pharmacology*
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Cell Cycle / drug effects
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
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Enzyme Activation / drug effects
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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G1 Phase / drug effects*
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Gene Expression Regulation, Enzymologic
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Humans
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Immunoblotting
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Immunoprecipitation
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Isoquinolines / pharmacology*
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / enzymology*
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Signal Transduction
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ras Proteins / genetics
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ras Proteins / metabolism*
Substances
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Alkaloids
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Benzophenanthridines
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Isoquinolines
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Cyclin-Dependent Kinase Inhibitor p27
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sanguinarine
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Extracellular Signal-Regulated MAP Kinases
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ras Proteins