Abstract
The inhibitory effects of apigenin on the growth factor-induced proliferative responses,
and expression of mitogen-activated protein (MAP) kinase and its downstream c-fos in rat aortic vascular smooth muscle cells (VSMCs) were investigated. Apigenin significantly
inhibited both 5 % fetal bovine serum (FBS)- and 50 ng/mL platelet derived growth
factor-BB (PDGF-BB)-induced proliferation on primary cultured rat VSMCs in a concentration-dependent
manner. In addition, apigenin resulted in a significant inhibition of the FBS-induced
phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and expression
of c-fos mRNA. These results suggest that apigenin inhibits FBS- and PDGF-BB-induced VSMC
proliferation, and its activity may be mediated, at least in part, by down regulation
of ERK 1/2 and its downstream c-fos mRNA.
Key words
Apigenin - vascular smooth muscle cell - cell proliferation - MAP kinase -
c-fos
References
- 1
Ross R.
The pathogenesis of arteriosclerosis: An update.
New England Journal of Medicine.
1986;
314
488-500
- 2
Ross R.
The pathogenesis of atherosclerosis: A perspective for the 1990’s.
Nature.
1993;
362
801-9
- 3
Davis R J.
The mitogen-activated protein kinase signal transduction pathway.
Journal of Biological Chemistry.
1993;
268
14 553-6
- 4 Lewis N G. Plant Phenolics. Antioxidants in Higher Plants. In: Alscher RG, Hess
JL, editors CRC Press Boca Raton, FL; 1993: 135-69
- 5 Ji Y B. Pharmacological action and application of blood activating and stasis-eliminating
available composition of Traditional Chinese Medicine. Publishing House of Sci Tech
HeilongJiang China; 1999: 22
- 6
Gerritsen M E, Carley W W, Ranges G E, Shen C P, Phan S A, Ligon G F . et al .
Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression.
American Journal of Pathology.
1995;
147
278-92
- 7
Capasso A, Pinto A, Sorrentino R, Capasso F.
Inhibitory effects of quercetin and other flavonoids on electrically-induced contractions
of guinea pig isolated ileum.
Journal of Ethnopharmacology.
1991;
34
279-81
- 8
Di Carlo G, Autore G, Izzo A A, Maiolino P, Mascolo N, Viola P . et al .
Inhibition of intestinal motility and secretion by flavonoids in mice and rats: Structure-activity
relationships.
Journal of Pharmacy and Pharmacology.
1993;
45
1054-9
- 9
Chamley-Campbell J, Campbell G R, Ross R.
The smooth muscle cell in culture.
Physiological Reviews.
1979;
59
1-61
- 10
Chomczynski P, Sacchi N.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform
extraction.
Analytical Biochemistry.
1987;
162
156-9
- 11
Lau K M, Leav I, Ho S M.
Rat estrogen receptor-α and -β, and progesterone receptor mRNA expression in various
prostatic lobes and microdissected normal and dysplastic epithelial tissues of the
noble rats.
Endocrinology.
1998;
139
424-7
- 12
Curran T, Gordon M B, Rubino K L, Sambucetti L C.
Isolation and characterization of the c-fos (rat) cDNA and analysis of post-transcriptional modification in vitro
.
Oncogene .
1987;
2
79-84
- 13
Fort P, Marty L, Piechaczyk M, Sabroutys D C, Jeanteur P, Blanchard J M.
Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate
dehydrogenase multigenic family.
Nucleic Acids Research.
1985;
13
1431-42
- 14
Ohlstein E H, Douglas S A, Sung C P, Yue T L, Louden C, Arleth A . et al .
Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation,
migration, and neointimal formation following vascular injury.
Proceedings of National Academy of Sciences of the USA.
1993;
90
6189-93
- 15
Ahn H Y, Hadizadeh K R, Seul C, Yun Y P, Vetter H, Sachinidis A.
Epigallocatechin 3-gallate selectively inhibits the PDGF-BB-induced intracellular
signaling transduction pathway in vascular smooth muscle cells and inhibits transformation
of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172).
Molecular Biology of the Cell.
1999;
10
1093-104
- 16 Zhang Y H, Park Y S, Kim T J, Fang L H, Ahn H Y, Hong J T . et al .Endothelium-dependent
vasorelaxant and antiproliferative effects of apigenin. General Pharmacology 2002
35: 341-7
- 17
Wennstrom S, Siegbahn A, Yokote K.
Membrane ruffling and chemotaxis transduced by the PDGF beta-receptor require the
binding site for phosphatidylinositol 3-kinase.
Oncogene.
1994;
9
651-60
- 18
Agullo G, Gamet-Payrastre L, Manenti S, Viala C, Remesy C, Chap H . et al .
Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase:
a comparison with tyrosine kinase and protein kinase C inhibition.
Biochemical Pharmacoloy..
1997;
53
1649-57
Yeo-Pyo Yun, Ph. D., Professor
College of Pharmacy
Chungbuk National University
48 Gaesin-Dong, Heungduk-Gu
Cheongju, 361-763
Republic of Korea
eMail: ypyun@cbucc.chungbuk.ac.kr
Fax: +82-43-268-2732
