title: Goniolactone C, a styryl lactone derivative, inhibits PDGF-BB-induced vascular smooth muscle cell migration and proliferation via PDGFR/ERK signaling.
abstract: Platelet-derived growth factor-BB (PDGF-BB) and its downstream effector, extracellular signal-regulated kinase 1/2 (ERK1/2) MAP kinase, initiate a multitude of biological effects, including vascular smooth muscle cell (VSMC) proliferation and migration, which are critical events in the initiation and development of restenosis following percutaneous transluminal coronary angioplasty (PTCA). Styryl lactones are natural products that have been demonstrated to possess anti-proliferative activities. Goniolactone C is a styryl lactone derivative that was first extracted from Goniothalamus cheliensis Hu. In the present study, we investigated the effects of goniolactone C on VSMC migration and proliferation. We found that goniolactone C preferentially interacted with cellular systems that rely on PDGF signaling but not those that rely on epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) signaling. Goniolactone C strongly inhibited PDGF-BB-induced VSMC migration and proliferation. goniolactone C-mediated inhibition of VSMC proliferation was associated with cell cycle arrest, while goniolactone C-mediated inhibition of VSMC migration was associated with the suppression of adhesion molecule expression. In addition, goniolactone C directly inhibited PDGFR-β kinase activity, thereby blocking the downstream effector of PDGF-BB. Thus, the results of the present study suggest a novel adjunctive pharmacological strategy that may be used to prevent angioplasty-related restenosis.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology and Critical Care medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China. dugh@imm.ac.cn.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000818:Animals; D000077214:Becaplermin; D015815:Cell Adhesion Molecules / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D044950:Flavanones; D007783:Lactones; D020574:Proto-Oncogene Proteins c-sis; C000599696:goniolactone C; D000077214:Becaplermin; C016063:pinocembrin; D017479:Receptors, Platelet-Derived Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases