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DOI: 10.1055/s-2002-32901
© Georg Thieme Verlag Stuttgart · New York
Effects of Apigenin on the Serum- and Platelet Derived Growth Factor-BB-Induced Proliferation of Rat Aortic Vascular Smooth Muscle Cells
Publikationsverlauf
Received: October 19, 2001
Accepted: February 3, 2002
Publikationsdatum:
22. Juli 2002 (online)
![](https://www.thieme-connect.de/media/plantamedica/200207/lookinside/thumbnails/10.1055-s-2002-32901-1.jpg)
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
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