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Article Open Access

Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways

  • Authors:
    • Ai‑Lei Wang
    • Yong Li
    • Qun Zhao
    • Li‑Qiao Fan
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 7721-7729
    |
    Published online on: April 5, 2018
       https://doi.org/10.3892/mmr.2018.8857
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Abstract

Formononetin (Form), a phytoestrogen extracted from the roots of Astragalus membranaceus, is one of the fundamental herbs used in traditional Chinese medicine because of its protective effects against certain malignant tumors. However, its role in colon carcinoma cells and the underlying molecular mechanisms have not been completely elucidated. The present study aimed to demonstrate that Form significantly inhibited the proliferation and invasion of the colon carcinoma cell lines SW1116 and HCT116. Mechanistic studies have suggested that Form suppresses colon carcinoma cell growth by downregulating cell cycle‑associated protein (cyclin D1) expression and arresting the cell cycle at the G0‑G1 checkpoint. Further studies revealed that treatment with Form inhibits matrix metalloproteinase (MMP)2 and MMP9 expression. Aditionally, the results demonstrated that Form significantly increased microRNA (miR)‑149 expression. Following miR‑149 overexpression in SW1116 and HCT116 cells using an miR‑149 mimic, cell viability and Ephrin type‑B receptor 3 (EphB3) levels decreased. Furthermore, the inhibitory effects of Form were associated with phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. These results indicated the suppressive effect of Form on colon carcinoma cell proliferation and invasion, possibly via miR‑149‑induced EphB3 downregulation and the inhibition of the PI3K/AKT and STAT3 signaling pathways. Overall, Form may be used as a novel candidate for the clinical treatment of colorectal cancer in the future.
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View References

1 

Bodalal Z and Bendardaf R: Coloectal carcinoma in aSouthern Mediterranean country: The Libyan scenario. World J Gastrointest Oncol. 6:98–103. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Touil Y, Igoudjil W, Corvaisier M, Dessein AF, Vandomme J, Monté D, Stechly L, Skrypek N, Langlois C, Grard G, et al: Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis. Clin Cancer Res. 20:837–846. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, et al: Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 486:532–536. 2012. 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 

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

6 

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

7 

Barbato S, Solaini G and Fabbri M: MicroRNAs in oncogenesis and tumor suppression. Int Rev Cell Mol Biol. 333:229–268. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP and Burge CB: Prediction of mammalian microRNA targets. Cell. 115:787–798. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Wu Y, Zhang X, Li Z, Yan H, Qin J and Li T: Formononetin inhibits human bladder cancer cell proliferation and invasiveness via regulation of miR-21 and PTEN. Food Funct. 8:1061–1066. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Hu W and Xiao Z: Formononetin induces apoptosis of human osteosarcoma cell line U2OS by regulating the expression of Bcl-2, Bax and MiR-375 in vitro and in vivo. Cell Physiol Biochem. 37:933–939. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Chen J, Zhang X, Wang Y, Ye Y and Huang Z: Formononetin promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in estrogen receptor-positive cells. Mol Carcinog. 55:312–319. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Zhang G, Liu X, Li Y, Wang Y, Liang H, Li K, Li L, Chen C, Sun W, Ren S, et al: EphB3-targeted regulation of miR-149 in the migration and invasion of human colonic carcinoma HCT116 and SW620 cells. Cancer Sci. 108:408–418. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Huang J, Xie M, Gao P, Ye Y, Liu Y, Zhao Y, Luo W, Ling Z, Cao Y, Zhang S, et al: Antiproliferative effects of formononetin on human colorectal cancer via, suppressing cell growth in vitro, and in vivo. Process Biochem. 50:912–917. 2015. View Article : Google Scholar

14 

Auyeung KK, Law PC and Ko JK: Novel anti-angiogenic effects of formononetin in human colon cancer cells and tumor xenograft. Oncol Rep. 28:2188–2194. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Chen J, Zeng J, Xin M, Huang W and Chen X: Formononetin induces cell cycle arrest of human breast cancer cells via IGF1/PI3K/Akt pathways in vitro and in vivo. Horm Metab Res. 43:681–686. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Begnini KR, de Leon Moura PM, Thurow H, Schultze E, Campos VF, Rodrigues Martins F, Borsuk S, Dellagostin OA, Savegnago L, Roesch-Ely M, et al: Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells. Evid Based Complement Alternat Med. 2014:6398562014. View Article : Google Scholar : PubMed/NCBI

17 

Li G, Ji XD, Gao H, Zhao JS, Xu JF, Sun ZJ, Deng YZ, Shi S, Feng YX, Zhu YQ, et al: EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex. Nat Commun. 3:6672012. View Article : Google Scholar : PubMed/NCBI

18 

Chen J and Sun L: Formononetin-induced apoptosis by activation of Ras/p38 mitogen-activated protein kinase in estrogen receptor-positive human breast cancer cells. Horm Metab Res. 44:943–948. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Galliher AJ and Schiemann WP: Src phosphorylates Tyr284 in TGF-beta type II receptor and regulates TGF-beta stimulation of p38 MAPK during breast cancer cell proliferation and invasion. Cancer Res. 67:3752–3758. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Sun M, Liu C, Nadiminty N, Lou W, Zhu Y, Yang J, Evans CP, Zhou Q and Gao AC: Inhibition of Stat3 activation by sanguinarine suppresses prostate cancer cell growth and invasion. Prostate. 72:82–89. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Ko JK, Lam FY and Cheung AP: Amelioration of experimental colitis by Astragalus membranaceus through anti-oxidation and inhibition of adhesion molecule synthesis. World J Gastroenterol. 11:5787–5794. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Auyeung KK and Ko JK: Novel herbal flavonoids promote apoptosis but differentially induce cell cycle arrest in human colon cancer cell. Invest New Drugs. 28:1–13. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Wang F, Ma YL, Zhang P, Shen TY, Shi CZ, Yang YZ, Moyer MP, Zhang HZ, Chen HQ, Liang Y and Qin HL: SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J Pathol. 229:12–24. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Liu X, Xie T, Mao X, Xue L, Chu X and Chen L: MicroRNA-149 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by targeting forkhead box transcription factor FOXM1. Cell Physiol Biochem. 39:617–629. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Wu XY, Xu H, Wu ZF, Chen C, Liu JY, Wu GN, Yao XQ, Liu FK, Li G and Shen L: Formononetin, a novel FGFR2 inhibitor, potently inhibits angiogenesis and tumor growth in preclinical models. Oncotarget. 6:44563–44578. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Nicholson KM and Anderson NG: The protein kinase B/Akt signaling pathway in human malignancy. Cell Signal. 14:381–395. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Liabakk NB, Talbot I, Smith RA, Wilkinson K and Balkwill F: Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res. 56:190–196. 1996.PubMed/NCBI

28 

Timofeeva OA, Tarasova NI, Zhang X, Chasovskikh S, Cheema AK, Wang H, Brown ML and Dritschilo A: STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain. Proc Natl Acad Sci USA. 110:1267–1272. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang AL, Li Y, Zhao Q and Fan LQ: Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Mol Med Rep 17: 7721-7729, 2018.
APA
Wang, A., Li, Y., Zhao, Q., & Fan, L. (2018). Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Molecular Medicine Reports, 17, 7721-7729. https://doi.org/10.3892/mmr.2018.8857
MLA
Wang, A., Li, Y., Zhao, Q., Fan, L."Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways". Molecular Medicine Reports 17.6 (2018): 7721-7729.
Chicago
Wang, A., Li, Y., Zhao, Q., Fan, L."Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways". Molecular Medicine Reports 17, no. 6 (2018): 7721-7729. https://doi.org/10.3892/mmr.2018.8857
Copy and paste a formatted citation
x
Spandidos Publications style
Wang AL, Li Y, Zhao Q and Fan LQ: Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Mol Med Rep 17: 7721-7729, 2018.
APA
Wang, A., Li, Y., Zhao, Q., & Fan, L. (2018). Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Molecular Medicine Reports, 17, 7721-7729. https://doi.org/10.3892/mmr.2018.8857
MLA
Wang, A., Li, Y., Zhao, Q., Fan, L."Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways". Molecular Medicine Reports 17.6 (2018): 7721-7729.
Chicago
Wang, A., Li, Y., Zhao, Q., Fan, L."Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways". Molecular Medicine Reports 17, no. 6 (2018): 7721-7729. https://doi.org/10.3892/mmr.2018.8857
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