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Article

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

  • Authors:
    • Zhuo Chen
    • Suixin Liu
    • Ying Cai
    • Kangling Xie
    • Wenliang Zhang
    • Lei Dong
    • Yuan Liu
    • Fan Zheng
    • Yaoshan Dun
    • Ning Li
  • View Affiliations / Copyright

    Affiliations: Department of Rehabilitation, Cardiac Rehabilitation Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
  • Pages: 1901-1907
    |
    Published online on: July 13, 2016
       https://doi.org/10.3892/etm.2016.3514
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Abstract

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia‑induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet‑derived growth factor (PDGF)‑BB‑induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF‑BB‑induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF‑BB‑induced upregulation of cell cycle‑related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF‑BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF‑BB‑stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.
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1 

Rodríguez AI, Csányi G, Ranayhossaini DJ, Feck DM, Blose KJ, Assatourian L, Vorp DA and Pagano PJ: MEF2B-Nox1 signaling is critical for stretch-induced phenotypic modulation of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 35:430–438. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Chiong M, Cartes-Saavedra B, Norambuena-Soto I, Mondaca-Ruff D, Morales PE, García-Miguel M and Mellado R: Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation. Front Cell Dev Biol. 2:722014. View Article : Google Scholar : PubMed/NCBI

3 

Choe N, Kwon JS, Kim JR, Eom GH, Kim Y, Nam KI, Ahn Y, Kee HJ and Kook H: The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia. Atherosclerosis. 229:348–355. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Jin M, Zhao K, Huang Q and Shang P: Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol. 64:257–266. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Agyemang K, Han L, Liu E, Zhang Y, Wang T and Gao X: Recent Advances in Astragalus membranaceus anti-diabetic research: Pharmacological effects of its phytochemical constituents. Evid Based Complement Alternat Med. 2013:6546432013. View Article : Google Scholar : PubMed/NCBI

6 

Zhang J, Xie X, Li C and Fu P: Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models. J Ethnopharmacol. 126:189–196. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Wu F and Chen X: A review of pharmacological study on Astragalus membranaceus (Fisch.) Bge. Zhong Yao Cai. 27:232–234. 2004.(In Chinese). PubMed/NCBI

8 

Li T, Zhao X, Mo Z, Huang W, Yan H, Ling Z and Ye Y: Formononetin promotes cell cycle arrest via downregulation of Akt/Cyclin D1/CDK4 in human prostate cancer cells. Cell Physiol Biochem. 34:1351–1358. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Zhou R, Xu L, Ye M, Liao M, Du H and Chen H: Formononetin inhibits migration and invasion of MDA-MB-231 and 4T1 breast cancer cells by suppressing MMP-2 and MMP-9 through PI3K/AKT signaling pathways. Horm Metab Res. 46:753–760. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Zhang X, Bi L, Ye Y and Chen J: Formononetin induces apoptosis in PC-3 prostate cancer cells through enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway. Nutr Cancer. 66:656–661. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Jia WC, Liu G, Zhang CD and Zhang SP: Formononetin attenuates hydrogen peroxide (H2O2)-induced apoptosis and NF-κB activation in RGC-5 cells. Eur Rev Med Pharmacol Sci. 18:2191–2197. 2014.PubMed/NCBI

12 

Liang K, Ye Y, Wang Y, Zhang J and Li C: Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway. J Neurol Sci. 344:100–104. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Huh JE, Nam DW, Baek YH, Kang JW, Park DS, Choi DY and Lee JD: Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways. Int Immunopharmacol. 11:46–54. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Zhu H, Zou L, Tian J, Lin F, He J and Hou J: Protective effects of sulphonated formononetin in a rat model of cerebral ischemia and reperfusion injury. Planta Med. 80:262–268. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Lee MH, Kwon BJ, Seo HJ, Yoo KE, Kim MS, Koo MA and Park JC: Resveratrol inhibits phenotype modulation by platelet derived growth factor-bb in rat aortic smooth muscle cells. Oxid Med Cell Longev. 2014:5724302014. View Article : Google Scholar : PubMed/NCBI

16 

Chen Z, Cai Y, Zhang W, Liu X and Liu S: Astragaloside IV inhibits platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells via the inhibition of p38 MAPK signaling. Exp Ther Med. 8:1253–1258. 2014.PubMed/NCBI

17 

Guan BZ, Yan RL, Huang JW, Li FL, Zhong YX, Chen Y, Liu FN, Hu B, Huang SB and Yin LH: Activation of G Protein coupled estrogen receptor (GPER) promotes the migration of renal cell carcinoma via the PI3K/AKT/MMP-9 signals. Cell Adh Migr 0. 2015. View Article : Google Scholar

18 

Salabei JK and Hill BG: Autophagic regulation of smooth muscle cell biology. Redox Biol. 4:97–103. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Qiu J, Zheng Y, Hu J, Liao D, Gregersen H, Deng X, Fan Y and Wang G: Biomechanical regulation of vascular smooth muscle cell functions: From in vitro to in vivo understanding. J R Soc Interface. 11:201308522013. View Article : Google Scholar : PubMed/NCBI

20 

Li H, Luo K and Hou J: Inhibitory effect of Puerariae radix flavones on platelet-derived growth factor-BB-induced proliferation of vascular smooth muscle cells via PI3K and ERK pathways. Exp Ther Med. 9:257–261. 2015.PubMed/NCBI

21 

Guan S, Tang Q, Liu W, Zhu R and Li B: Nobiletin Inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in a rat carotid artery injury model. Drug Dev Res. 75:489–496. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Tolva V, Mazzola S, Zerbi P, Casana R, Albertini M, Calvillo L, Selmin F and Cilurzo F: A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon. J Vasc Surgp. ii:S0741–S5214. 2014.

23 

Liu Y, He J, Chen X, Li J, Shen M, Yu W, Yang Y and Xiao Z: The proapoptotic effect of formononetin in human osteosarcoma cells: Involvement of inactivation of ERK and Akt pathways. Cell Physiol Biochem. 34:637–645. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Huang X, Jin Y, Zhou D, Xu G, Huang J and Shen L: IQGAP1 promotes the phenotypic switch of vascular smooth muscle by myocardin pathway: A potential target for varicose vein. Int J Clin Exp Pathol. 7:6475–6485. 2014.PubMed/NCBI

25 

Song Y, Long L, Zhang N and Liu Y: Inhibitory effects of hydroxysafflor yellow A on PDGF-BB-induced proliferation and migration of vascular smooth muscle cells via mediating Akt signaling. Mol Med Rep. 10:1555–1560. 2014.PubMed/NCBI

26 

Song MC, Park J and Kim TJ: Diethylstilbestrol induces arrest of rat vascular smooth muscle cell cycle progression through downregulation of cyclin D1 and cyclin E. Mol Cell Biochem. 360:103–109. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Ding Q, Chai H, Mahmood N, Tsao J, Mochly-Rosen D and Zhou W: Matrix metalloproteinases modulated by protein kinase Cε mediate resistin-induced migration of human coronary artery smooth muscle cells. J Vasc Surg. 53:1044–1051. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Guo L, Ning W, Tan Z, Gong Z and Li X: Mechanism of matrix metalloproteinase axis-induced neointimal growth. J Mol Cell Cardiol. 66:116–125. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Toker A: Achieving specificity in Akt signaling in cancer. Adv Biol Regul. 52:78–87. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Vasudevan KM and Garraway LA: AKT signaling in physiology and disease. Curr Top Microbiol Immunol. 347:105–133. 2010.PubMed/NCBI

31 

Liu D, Liu J, Lin B, Liu S, Hou R, Hao Y, Liu Q, Zhang S and Iwamori M: Lewis y regulate cell cycle related factors in ovarian carcinoma cell RMG-I in vitro via ERK and Akt signaling pathways. Int J Mol Sci. 13:828–839. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Park ES, Kang SI, Yoo KD, Lee MY, Yoo HS, Hong JT, Shin HS, Kim B and Yun YP: Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway. Exp Cell Res. 319:982–991. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Iida M, Tanabe K, Kozawa O and Iida H: Differential effects of intravenous anesthetics on PDGF-BB-induced vascular smooth muscle cell migration. Cell Physiol Biochem. 33:1827–1837. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Son JE, Jeong H, Kim H, Kim YA, Lee E, Lee HJ and Lee KW: Pelargonidin attenuates PDGF-BB-induced aortic smooth muscle cell proliferation and migration by direct inhibition of focal adhesion kinase. Biochem Pharmacol. 89:236–245. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen Z, Liu S, Cai Y, Xie K, Zhang W, Dong L, Liu Y, Zheng F, Dun Y, Li N, Li N, et al: Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells. Exp Ther Med 12: 1901-1907, 2016.
APA
Chen, Z., Liu, S., Cai, Y., Xie, K., Zhang, W., Dong, L. ... Li, N. (2016). Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells. Experimental and Therapeutic Medicine, 12, 1901-1907. https://doi.org/10.3892/etm.2016.3514
MLA
Chen, Z., Liu, S., Cai, Y., Xie, K., Zhang, W., Dong, L., Liu, Y., Zheng, F., Dun, Y., Li, N."Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells". Experimental and Therapeutic Medicine 12.3 (2016): 1901-1907.
Chicago
Chen, Z., Liu, S., Cai, Y., Xie, K., Zhang, W., Dong, L., Liu, Y., Zheng, F., Dun, Y., Li, N."Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1901-1907. https://doi.org/10.3892/etm.2016.3514
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Z, Liu S, Cai Y, Xie K, Zhang W, Dong L, Liu Y, Zheng F, Dun Y, Li N, Li N, et al: Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells. Exp Ther Med 12: 1901-1907, 2016.
APA
Chen, Z., Liu, S., Cai, Y., Xie, K., Zhang, W., Dong, L. ... Li, N. (2016). Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells. Experimental and Therapeutic Medicine, 12, 1901-1907. https://doi.org/10.3892/etm.2016.3514
MLA
Chen, Z., Liu, S., Cai, Y., Xie, K., Zhang, W., Dong, L., Liu, Y., Zheng, F., Dun, Y., Li, N."Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells". Experimental and Therapeutic Medicine 12.3 (2016): 1901-1907.
Chicago
Chen, Z., Liu, S., Cai, Y., Xie, K., Zhang, W., Dong, L., Liu, Y., Zheng, F., Dun, Y., Li, N."Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1901-1907. https://doi.org/10.3892/etm.2016.3514
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