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Molecules 2014, 19(12), 19501-19515; doi:10.3390/molecules191219501

Goniolactone C, a Styryl Lactone Derivative, Inhibits PDGF-BB-Induced Vascular Smooth Muscle Cell Migration and Proliferation via PDGFR/ERK Signaling

1,2, 1,3, 4, 1, 1 and 1,2,*
1
Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China
2
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Beijing 100050, China
3
State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China
4
Department of Anesthesiology and Critical Care medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
*
Author to whom correspondence should be addressed.
Received: 21 September 2014 / Revised: 24 October 2014 / Accepted: 24 October 2014 / Published: 26 November 2014
(This article belongs to the Section Medicinal Chemistry)
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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. View Full-Text
Keywords: styryl lactones; goniolactone C; VSMC; proliferation; migration; PDGF-BB styryl lactones; goniolactone C; VSMC; proliferation; migration; PDGF-BB
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sun, L.; Zhao, R.; Lan, X.; Chen, R.; Wang, S.; Du, G. Goniolactone C, a Styryl Lactone Derivative, Inhibits PDGF-BB-Induced Vascular Smooth Muscle Cell Migration and Proliferation via PDGFR/ERK Signaling. Molecules 2014, 19, 19501-19515.

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