naphthoquinones and Coronary-Restenosis

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-Rβ or Akt, it did inhibit the phosphorylation of Erk1/2 and PLCγ1 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 U73122, a PLCγ 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.

Topics: Animals; Cell Proliferation; Cells, Cultured; Coronary Restenosis; G1 Phase; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Naphthoquinones; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Receptor, Platelet-Derived Growth Factor beta; Resting Phase, Cell Cycle; Retinoblastoma Protein

Topics: Animals; Cardiovascular Agents; Carotid Stenosis; Cell Proliferation; Coronary Restenosis; Drug-Eluting Stents; Enzyme Activation; Enzyme Activators; Humans; Hyperplasia; Muscle, Smooth, Vascular; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Secondary Prevention; Tunica Intima