Inhibition of mitogen-mediated proliferation of rat vascular smooth muscle cells by labedipinedilol-A through PKC and ERK 1/2 pathway

Shu Fen Liou, Jwu Lai Yeh, Jyh Chong Liang, Chaw Chi Chiu, Young Tso Lin, Ing Jun Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Labedipinedilol-A is a novel 1, 4-dihydropyridine type calcium antagonist with alpha-receptor blocking activity. This study investigates the effects of labedipinedilol-A on mitogen-induced proliferation of rat vascular smooth muscle cells (VSMCs). Labedipinedilol-A's inhibition on cell proliferation was measured by the tetrazolium salt (XTT) test. Labedipinedilol-A dose-dependently inhibited mitogen-induced DNA synthesis, determined by the incorporation of 5-bromo-2′-deoxyuridine (BrdU). Labedipinedilol-A was also found capable of inhibiting the migration of VSMCs induced by PDGF-BB with an IC50 value of 5.6 μM. In accordance with these findings, labedipinedilol-A revealed blocking of the FBS-inducible progression through G0/G 1 to S phase of the cell cycle in synchronized cells. Labedipinedilol-A appeared to cause inhibition of mitogens-induced PKC translocation, suggesting the probable involvement of protein kinase C (PKC) in this cellular response. Labedipinedilol-A reduced both intracellular Ca 2+ and the phosphorylation of extracellular signal-regulated protein kinase 1/2 in PDGF-BB-stimulated VSMCs. It also suppressed the levels of proliferative cell nuclear antigen (PCNA) in VSMCs both time- and dose-dependently. These results indicate that labedipinedilol-A may inhibit cell proliferation by attenuating activation of the ERK 1/2 pathway, which is regulated by PKC and Ca2+, suggesting that it may have great potential in the prevention of progressive atherosclerosis.

Original languageEnglish
Pages (from-to)539-551
Number of pages13
JournalJournal of Cardiovascular Pharmacology
Volume44
Issue number5
DOIs
Publication statusPublished - 2004 Nov
Externally publishedYes

Keywords

  • ERK 1/2
  • Labedipinedilol-A
  • PCNA
  • PKC
  • Pyk2
  • Rat vascular smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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