5,8-Dimethoxy-2-Nonylamino-Naphthalene-1,4-Dione Inhibits Vascular Smooth Muscle Cell Proliferation by Blocking Autophosphorylation of PDGF-Receptor beta.
10.4196/kjpp.2013.17.3.203
- Author:
Yohan KIM
1
;
Jung Jin LEE
;
Sang Gil LEE
;
Sang Hyuk JUNG
;
Joo Hui HAN
;
So Young YANG
;
Eunju YUN
;
Gyu Yong SONG
;
Chang Seon MYUNG
Author Information
1. Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. cm8r@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
2-Nonylamino-DMNQ;
Cardiovascular diseases;
Platelet-derived growth factor receptor-beta;
Proliferation;
Vascular smooth muscle cell
- MeSH:
Atherosclerosis;
Cardiovascular Diseases;
Cell Count;
Cell Cycle;
Cell Proliferation;
Cyclins;
Epidermal Growth Factor;
Muscle, Smooth, Vascular;
Phosphorylation;
Phosphotransferases;
Platelet-Derived Growth Factor;
Proliferating Cell Nuclear Antigen;
S Phase
- From:The Korean Journal of Physiology and Pharmacology
2013;17(3):203-208
- CountryRepublic of Korea
- Language:English
-
Abstract:
As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced [3H]-thymidine incorporation, cell cycle progression from G0/G1 to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptorbeta(PDGF-Rbeta) enhanced by PDGF at Tyr579, Tyr716, Tyr751, and Tyr1021 residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and PLCgamma1. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-Rbeta autophosphorylation, and subsequently PDGF-Rbeta-mediated downstream signaling pathways.
