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 language | English |
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Pages (from-to) | 539-551 |
Number of pages | 13 |
Journal | Journal of Cardiovascular Pharmacology |
Volume | 44 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2004 Nov |
Externally published | Yes |
Keywords
- ERK 1/2
- Labedipinedilol-A
- PCNA
- PKC
- Pyk2
- Rat vascular smooth muscle cells
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine