title: Fangchinoline inhibits rat aortic vascular smooth muscle cell proliferation and cell cycle progression through inhibition of ERK1/2 activation and c-fos expression.
abstract: Fangchinoline (FAN; a plant alkaloid isolated from Stephania tetrandrae) is a nonspecific Ca(2+) channel blocker. The objective of the present study was to investigate the effect of FAN on the growth factor-induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). FAN significantly inhibited both 5% fetal bovine serum (FBS)- and 50ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation, [3H]thymidine incorporation into DNA and phosphorylation of extracellular signal-regulated kinase 1/2. In accordance with these findings, FAN revealed blocking of the FBS-inducible progression through G(0)/G(1) to S phase of the cell cycle in synchronized cells and caused a 62% decrease in the early elevation of c-fos expression induced after 5% FBS addition. Furthermore, significant antiproliferative activity of FAN is observed at concentrations below those required to achieve significant inhibition of Ca(2+) channels by FAN. These results suggest that FAN reduced both FBS- and PDGF-BB-induced RASMCs proliferation by perturbing cell cycle progression. This antiproliferative effect of FAN is dependent on the MAP kinase pathway, but cannot be limited to its Ca(2+) modulation.
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing, PR China. yhzhpku@bjmu.edu.cn
authors.forename: Yong-He
authors.initials: YH
authors.lastname: Zhang
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Fang
authors.forename: Bao-Shan
authors.initials: BS
authors.lastname: Ku
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D016760:Proto-Oncogene Proteins c-fos; D004247:DNA; C060802:fangchinoline; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases