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Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion

  • Authors:
    • Guodong Zhang
    • Lixiang He
    • Junhao Chen
    • Botao Xu
    • Zejun Mao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiothoracic Surgery, Zhuji People's Hospital, Zhuji, Zhejiang 311800, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2913-2922
    |
    Published online on: February 21, 2020
       https://doi.org/10.3892/etm.2020.8543
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Abstract

The efficacy of ginsenoside Rh2 (Rh2) in cancer therapy has been reported; however, its function in lung cancer remains unknown. To analyze the role of Rh2 in the inhibition of lung cancer cell proliferation in the present study, protein expression levels of E‑cadherin, vimentin, β‑catenin, Smo, Gli1, and α‑catenin were assessed by western blotting, whilst mRNA expression levels of TCF7 FZD8, Smo, Gli1, Gli2, and Gli3 were determined by reverse transcription‑quantitative PCR in the A549 cell line. Phosphorylation sites were detected by proteomic methods and cell proliferation was analyzed by MTT assay. The present study revealed that Rh2 treatment significantly inhibited cell proliferation. Western blotting indicated that the expression levels of E‑cadherin were increased and vimentin was downregulated in Rh2‑treated cells compared with control cells. Treatment of A549 cells with Rh2 suppressed phosphorylation of five distinct proteins and increased phosphorylation of nine proteins. Among them, the phosphorylation of α‑catenin at S641 was significantly induced. Rh2 treatment suppressed the expression levels of key genes involved in Wnt (Wnt3, transcription factor 7 and frizzled class receptor 8) and hedgehog [smoothened, frizzled class receptor (Smo), GLI family zinc finger (Gli)1, Gli2, and Gli3] signaling. Immunoblotting results indicated that β‑catenin, Smo and Gli1 protein expression levels were also suppressed by treatment with Rh2 compared with control treatment. Expression of α‑catenin S641D, a phosphomimetic form of α‑catenin, inhibited the accumulation of β‑catenin and Gli1 and inhibited cell proliferation and invasion. Furthermore, knockdown of β‑catenin (CTNNB1) or Gli1 with specific small interfering RNAs inhibited cell proliferation, whereas overexpression of these genes had an opposite effect. Additionally, overexpression of β‑catenin or Gli1 activated cell proliferation, even in the presence of Rh2, suggesting that Rh2 affects A549 cell proliferation through inhibition of Wnt and hedgehog signaling by phosphorylation of α‑catenin at S641. Together, these data suggested that Rh2 treatment may inhibit the proliferation of A549 lung cancer cells. Further exploration of the underlying mechanism by which Rh2 inhibits cell proliferation is warranted.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016.PubMed/NCBI View Article : Google Scholar

2 

Chan BA and Hughes BG: Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl Lung Cancer Res. 4:36–54. 2015.PubMed/NCBI View Article : Google Scholar

3 

Roberts PJ, Stinchcombe TE, Der CJ and Socinski MA: Personalized medicine in non-small-cell lung cancer: Is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy? J Clin Oncol. 28:4769–4777. 2010.PubMed/NCBI View Article : Google Scholar

4 

de Looff M, de Jong S and Kruyt FA: The role of Src in TRAIL signaling in non-small cell lung cancer cells. Proceedings: AACR Annual Meeting 2018. April 14-18, 2018. Cancer Res 78: 4377, 2018.

5 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000.PubMed/NCBI View Article : Google Scholar

6 

Arbiser JL, Bonner MY and Gilbert LC: Targeting the duality of cancer. NPJ Precision Oncol 1: pii: 23, 017.

7 

Pfeffer CM and Singh ATK: Apoptosis: A target for anticancer therapy. Int J Mol Sci. 19(448)2018.PubMed/NCBI View Article : Google Scholar

8 

Rastogi V, Santiago-Moreno J and Doré S: Ginseng: A promising neuroprotective strategy in stroke. Front Cell Neurosci. 8(457)2015.PubMed/NCBI View Article : Google Scholar

9 

Kiefer D and Pantuso T: Panax ginseng. Am Fam Physician. 68:1539–1542. 2003.PubMed/NCBI

10 

Helms S: Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev. 9:259–274. 2004.PubMed/NCBI

11 

Fei XF, Wang BX, Tashiro S, Li TJ, Ma JS and Ikejima T: Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells. Acta Pharmacol Sin. 23:315–322. 2002.PubMed/NCBI

12 

Huang Y, Huang H, Han Z, Li W, Mai Z and Yuan R: Ginsenoside Rh2 inhibits angiogenesis in prostate cancer by targeting CNNM1. J Nanosci Nanotechnol. 19:1942–1950. 2019.PubMed/NCBI View Article : Google Scholar

13 

Chen WW, Huang YF, Hu ZB, Liu YM, Xiao HX, Liu DB and Zhuang YZ: Microarray analysis of altered long non-coding RNA expression profile in liver cancer cells treated by ginsenoside Rh2. J Asian Nat Prod Res. 21:742–753. 2019.PubMed/NCBI View Article : Google Scholar

14 

Lee H, Lee S, Jeong D and Kim SJ: Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells. J Ginseng Res. 42:455–462. 2018.PubMed/NCBI View Article : Google Scholar

15 

Li H, Huang N, Zhu W, Wu J, Yang X, Teng W, Tian J, Fang Z, Luo Y, Chen M and Li Y: Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2. BMC Cancer. 18(579)2018.PubMed/NCBI View Article : Google Scholar

16 

Wang Y, Xu H, Lu Z, Yu X, Lv C, Tian Y and Sui D: Pseudo-ginsenoside Rh2 induces A549 cells apoptosis via the Ras/Raf/ERK/p53 pathway. Exp Ther Med. 15:4916–4924. 2018.PubMed/NCBI View Article : Google Scholar

17 

Zhan T, Rindtorff N and Boutros M: Wnt signaling in cancer. Oncogene. 36:1461–1473. 2017.PubMed/NCBI View Article : Google Scholar

18 

Bushman W: Hedgehog signaling in development and cancer. In: Prostate cancer Springer, pp107-118, 2007.

19 

Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R and Ben-Ze'ev A: The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 96:5522–5527. 1999.PubMed/NCBI View Article : Google Scholar

20 

Moon RT, Kohn AD, De Ferrari GV and Kaykas A: WNT and beta-catenin signalling: Diseases and therapies. Nat Rev Genet. 5:691–701. 2004.PubMed/NCBI View Article : Google Scholar

21 

Clevers H: Wnt/β-catenin signaling in development and disease. Cell. 127:469–480. 2006.PubMed/NCBI View Article : Google Scholar

22 

Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C and Rando TA: Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 317:807–810. 2007.PubMed/NCBI View Article : Google Scholar

23 

Reya T and Clevers H: Wnt signalling in stem cells and cancer. Nature. 434:843–850. 2005.PubMed/NCBI View Article : Google Scholar

24 

Xin M, Ji X, De La Cruz LK, Thareja S and Wang B: Strategies to target the Hedgehog signaling pathway for cancer therapy. Med Res Rev. 38:870–913. 2018.PubMed/NCBI View Article : Google Scholar

25 

Beauchamp EM, Ringer L, Bulut G, Sajwan KP, Hall MD, Lee YC, Peaceman D, Ozdemirli M, Rodriguez O, Macdonald TJ, et al: Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway. J Clin Invest. 121:148–160. 2011.PubMed/NCBI View Article : Google Scholar

26 

Wang K, Pan L, Che X, Cui D and Li C: Sonic Hedgehog/GLI1 signaling pathway inhibition restricts cell migration and invasion in human gliomas. Neurol Res. 32:975–980. 2010.PubMed/NCBI View Article : Google Scholar

27 

Huangfu D and Anderson KV: Signaling from Smo to Ci/Gli: Conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development. 133:3–14. 2006.PubMed/NCBI View Article : Google Scholar

28 

Rohatgi R, Milenkovic L and Scott MP: Patched1 regulates hedgehog signaling at the primary cilium. Science. 317:372–376. 2007.PubMed/NCBI View Article : Google Scholar

29 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

30 

Larsen MR, Thigholm TE, Jensen ON, Roepstorff P and Jørgensen TJ: Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol Cell Proteomics. 4:873–886. 2005.PubMed/NCBI View Article : Google Scholar

31 

Xuan YH, Huang BB, Tian HS, Chi LS, Duan YM, Wang X, Zhu ZX, Cai WH, Zhu YT, Wei TM, et al: High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. PLoS One. 9(e108182)2014.PubMed/NCBI View Article : Google Scholar

32 

Tripathy A, Thakurela S, Sahu MK, Uthanasingh K, Behera M, Ajay AK and Kumari R: The molecular connection of histopathological heterogeneity in hepatocellular carcinoma: A role of Wnt and Hedgehog signaling pathways. PLoS One. 13(e0208194)2018.PubMed/NCBI View Article : Google Scholar

33 

Neal RD, Hamilton W and Rogers TK: Lung cancer. BMJ. 349(g6560)2014.PubMed/NCBI View Article : Google Scholar

34 

Piao HL, Yuan Y, Wang M, Sun Y, Liang H and Ma L: α-catenin acts as a tumour suppressor in E-cadherin-negative basal-like breast cancer by inhibiting NF-κB signalling. Nat Cell Biol. 16:245–254. 2014.PubMed/NCBI View Article : Google Scholar

35 

Wang Y, Lin P, Wang Q, Zheng M and Pang L: Wnt3a-regulated TCF4/β-catenin complex directly activates the key Hedgehog signalling genes Smo and GLI1. Exp Ther Med. 16:2101–2107. 2018.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Zhang G, He L, Chen J, Xu B and Mao Z: Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion. Exp Ther Med 19: 2913-2922, 2020.
APA
Zhang, G., He, L., Chen, J., Xu, B., & Mao, Z. (2020). Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion. Experimental and Therapeutic Medicine, 19, 2913-2922. https://doi.org/10.3892/etm.2020.8543
MLA
Zhang, G., He, L., Chen, J., Xu, B., Mao, Z."Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion". Experimental and Therapeutic Medicine 19.4 (2020): 2913-2922.
Chicago
Zhang, G., He, L., Chen, J., Xu, B., Mao, Z."Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion". Experimental and Therapeutic Medicine 19, no. 4 (2020): 2913-2922. https://doi.org/10.3892/etm.2020.8543
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G, He L, Chen J, Xu B and Mao Z: Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion. Exp Ther Med 19: 2913-2922, 2020.
APA
Zhang, G., He, L., Chen, J., Xu, B., & Mao, Z. (2020). Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion. Experimental and Therapeutic Medicine, 19, 2913-2922. https://doi.org/10.3892/etm.2020.8543
MLA
Zhang, G., He, L., Chen, J., Xu, B., Mao, Z."Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion". Experimental and Therapeutic Medicine 19.4 (2020): 2913-2922.
Chicago
Zhang, G., He, L., Chen, J., Xu, B., Mao, Z."Ginsenoside Rh2 activates α‑catenin phosphorylation to inhibit lung cancer cell proliferation and invasion". Experimental and Therapeutic Medicine 19, no. 4 (2020): 2913-2922. https://doi.org/10.3892/etm.2020.8543
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