Sanguinarine-induced G1-phase arrest of the cell cycle results from increased p27KIP1 expression mediated via activation of the Ras/ERK signaling pathway in vascular smooth muscle cells.
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.
Lee
Beobyi
B
Department of Anatomy, College of Medicine, Konkuk University, Chungju City, Chungbuk 380-701, South Korea.
Lee
Se-Jung
SJ
Park
Sung-Soo
SS
Kim
Si-Kwan
SK
Kim
Sung-Ryong
SR
Jung
Jae-Hyun
JH
Kim
Wun-Jae
WJ
Moon
Sung-Kwon
SK
D000470:Alkaloids / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D053119:Benzophenanthridines / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007546:Isoquinolines / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D000470:Alkaloids; D053119:Benzophenanthridines; D007546:Isoquinolines; D050760:Cyclin-Dependent Kinase Inhibitor p27; C005705:sanguinarine; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins