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Title: Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells

Abstract

Highlights: {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner with no apparent cytotoxicity. {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced phosphorylation of Erk1/2 and PLC{gamma}1. {yields} 2-Decylamino-DMNQ arrested a G{sub 0}/G{sub 1} cell cycle progression in association with pRb phosphorylation and PCNA expression. {yields} Both U0126, an Erk inhibitor, and U73122, a PLC{gamma} inhibitor, arrested a G{sub 0}/G{sub 1} phase of the cell cycle. -- Abstract: 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{sub 0}/G{sub 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,more » and U73122, a PLC{gamma} inhibitor, increased the proportion of cells in the G{sub 0}/G{sub 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{sub 0}/G{sub 1} phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.« less

Authors:
 [1];  [2]; ; ; ;  [1]; ;  [3];  [1];  [2]
  1. Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Medicinal Chemistry, Chungnam National University College of Pharmacy, Daejeon 305-764 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22207411
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 411; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; CATTLE; CELL CYCLE; CELL PROLIFERATION; CORONARIES; DMSO; DNA; ELECTROPHORESIS; GELS; GROWTH FACTORS; IODIDES; MUSCLES; PHOSPHATES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; RECEPTORS; SODIUM; SULFATES; TOXICITY

Citation Formats

Lee, Jung-Jin, Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Zhang, Wei-Yun, Yi, Hyoseok, Kim, Yohan, Kim, In-Su, Shen, Gui-Nan, Song, Gyu-Yong, Myung, Chang-Seon, E-mail: cm8r@cnu.ac.kr, and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764. Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.06.145.
Lee, Jung-Jin, Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Zhang, Wei-Yun, Yi, Hyoseok, Kim, Yohan, Kim, In-Su, Shen, Gui-Nan, Song, Gyu-Yong, Myung, Chang-Seon, E-mail: cm8r@cnu.ac.kr, & Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764. Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells. United States. doi:10.1016/J.BBRC.2011.06.145.
Lee, Jung-Jin, Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Zhang, Wei-Yun, Yi, Hyoseok, Kim, Yohan, Kim, In-Su, Shen, Gui-Nan, Song, Gyu-Yong, Myung, Chang-Seon, E-mail: cm8r@cnu.ac.kr, and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764. Fri . "Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells". United States. doi:10.1016/J.BBRC.2011.06.145.
@article{osti_22207411,
title = {Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells},
author = {Lee, Jung-Jin and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764 and Zhang, Wei-Yun and Yi, Hyoseok and Kim, Yohan and Kim, In-Su and Shen, Gui-Nan and Song, Gyu-Yong and Myung, Chang-Seon, E-mail: cm8r@cnu.ac.kr and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764},
abstractNote = {Highlights: {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner with no apparent cytotoxicity. {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced phosphorylation of Erk1/2 and PLC{gamma}1. {yields} 2-Decylamino-DMNQ arrested a G{sub 0}/G{sub 1} cell cycle progression in association with pRb phosphorylation and PCNA expression. {yields} Both U0126, an Erk inhibitor, and U73122, a PLC{gamma} inhibitor, arrested a G{sub 0}/G{sub 1} phase of the cell cycle. -- Abstract: 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{sub 0}/G{sub 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 PLC{gamma} inhibitor, increased the proportion of cells in the G{sub 0}/G{sub 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{sub 0}/G{sub 1} phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.},
doi = {10.1016/J.BBRC.2011.06.145},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 411,
place = {United States},
year = {Fri Jul 22 00:00:00 EDT 2011},
month = {Fri Jul 22 00:00:00 EDT 2011}
}