Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 411, Issue 1, Pages 213-218Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.06.145
Keywords
Cell cycle; Naphthoquinone; Restenosis; Vascular smooth muscle cell
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Funding
- Ministry of Education, Science, and Technology [2009-0093815]
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Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-R beta. or Akt, it did inhibit the phosphorylation of Erk1/2 and PLC gamma 1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G(0)/G(1) phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and 1373122, a PLC gamma inhibitor, increased the proportion of cells in the G(0)/G(1) phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G(0)/G(1) phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation. (C) 2011 Elsevier Inc. All rights reserved.
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