Suppression of LPS-induced epithelial-mesenchymal transition by aqueous extracts of Prunella vulgaris through inhibition of the NF-κB/Snail signaling pathway and regulation of EMT-related protein expression

  • Authors:
    • In-Hye Cho
    • Eun Hyang Jang
    • Darong Hong
    • Bom Jung
    • Min-Ju Park
    • Jong-Ho Kim
  • View Affiliations

  • Published online on: August 21, 2015     https://doi.org/10.3892/or.2015.4218
  • Pages: 2445-2450
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Prunella vulgaris (PV) inhibits the proliferation of various cancer cells; however, its possible role in EMT has not been demonstrated. In the present study, we explored the effect of PV aqueous extract (PVAE), a typical medicine for decoction, on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotype changes in cancer cell lines that enhanced cell migration and invasion. PVAE markedly inhibited these effects and produced accompanying changes in the expression of EMT markers, including decreased expression of N-cadherin and vimentin, and increased expression of β-catenin. We found that PVAE effects on LPS-induced EMT were mediated by inhibition of the NF-κB/Snail signaling pathway. Our findings provide new evidence that PVAE suppresses cancer invasion and migration by inhibiting EMT. Therefore, we suggest that PVAE is an effective dietary chemopreventive agent with antimetastatic activity against malignant tumors.

References

1 

Kong D, Li Y, Wang Z and Sarkar FH: Cancer stem cells and epithelial-to-mesenchymal transition (EMT)-phenotypic cells: Are They Cousins or Twins? Cancers (Basel). 3:716–729. 2011. View Article : Google Scholar

2 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Polyak K and Weinberg RA: Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nat Rev Cancer. 9:265–273. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Xu HX, Lee SH, Lee SF, White RL and Blay J: Isolation and characterization of an anti-HSV polysaccharide from Prunella vulgaris. Antiviral Res. 44:43–54. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Hwang YJ, Lee EJ, Kim HR and Hwang KA: In vitro antioxidant and anticancer effects of solvent fractions from Prunella vulgaris var. lilacina. BMC Complement Altern Med. 13:3102013. View Article : Google Scholar : PubMed/NCBI

6 

Park SH, Koo HJ, Sung YY and Kim HK: The protective effect of Prunella vulgaris ethanol extract against vascular inflammation in TNF-α-stimulated human aortic smooth muscle cells. BMB Rep. 46:352–357. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Psotová J, Kolár M, Sousek J, Svagera Z, Vicar J and Ulrichová J: Biological activities of Prunella vulgaris extract. Phytother Res. 17:1082–1087. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Yoon MY, Choi GJ, Choi YH, Jang KS, Park MS, Cha B and Kim JC: Effect of polyacetylenic acids from Prunella vulgaris on various plant pathogens. Lett Appl Microbiol. 51:511–517. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Choi JH, Han EH, Hwang YP, Choi JM, Choi CY, Chung YC, Seo JK and Jeong HG: Suppression of PMA-induced tumor cell invasion and metastasis by aqueous extract isolated from Prunella vulgaris via the inhibition of NF-kappaB-dependent MMP-9 expression. Food Chem Toxicol. 48:564–571. 2010. View Article : Google Scholar

10 

Kim SH, Huang CY, Tsai CY, Lu SY, Chiu CC and Fang K: The aqueous extract of Prunella vulgaris suppresses cell invasion and migration in human liver cancer cells by attenuating matrix metalloproteinases. Am J Chin Med. 40:643–656. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Chen MC, Chang WW, Kuan YD, Lin ST, Hsu HC and Lee CH: Resveratrol inhibits LPS-induced epithelial-mesenchymal transition in mouse melanoma model. Innate Immun. 18:685–693. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Huang T, Chen Z and Fang L: Curcumin inhibits LPS-induced EMT through downregulation of NF-κB-Snail signaling in breast cancer cells. Oncol Rep. 29:117–124. 2013.

13 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Herschkowitz JI, Zhao W, Zhang M, Usary J, Murrow G, Edwards D, Knezevic J, Greene SB, Darr D, Troester MA, et al: Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells. Proc Natl Acad Sci USA. 109:2778–2783. 2012. View Article : Google Scholar :

15 

Iliopoulos D, Lindahl-Allen M, Polytarchou C, Hirsch HA, Tsichlis PN and Struhl K: Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol Cell. 39:761–772. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, Chen ZQ, Liu XP and Xu ZD: Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 15:2657–2665. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM and Zhou BP: Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 15:416–428. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Kim HI, Quan FS, Kim JE, Lee NR, Kim HJ, Jo SJ, Lee CM, Jang DS and Inn KS: Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina. Biochem Biophys Res Commun. 451:282–287. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Blinman P, Alam M, Duric V, McLachlan SA and Stockler MR: Patients' preferences for chemotherapy in non-small-cell lung cancer: A systematic review. Lung Cancer. 69:141–147. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Feng L, Jia X, Zhu M, Chen Y and Shi F: Chemoprevention by Prunella vulgaris L. extract of non-small cell lung cancer via promoting apoptosis and regulating the cell cycle. Asian Pac J Cancer Prev. 11:1355–1358. 2010.

21 

Feng L, Jia XB, Jiang J, Zhu MM, Chen Y, Tan XB and Shi F: Combination of active components enhances the efficacy of Prunella in prevention and treatment of lung cancer. Molecules. 15:7893–7906. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Xu Y, Jiang Z, Ji G and Liu J: Inhibition of bone metastasis from breast carcinoma by rosmarinic acid. Planta Med. 76:956–962. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Xu Y, Xu G, Liu L, Xu D and Liu J: Anti-invasion effect of rosmarinic acid via the extracellular signal-regulated kinase and oxidation-reduction pathway in Ls174-T cells. J Cell Biochem. 111:370–379. 2010. View Article : Google Scholar : PubMed/NCBI

24 

van Roy F and Berx G: The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 65:3756–3788. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Nguyen PT, Kudo Y, Yoshida M, Kamata N, Ogawa I and Takata T: N-cadherin expression is involved in malignant behavior of head and neck cancer in relation to epithelial-mesenchymal transition. Histol Histopathol. 26:147–156. 2011.

26 

Araki K, Shimura T, Suzuki H, Tsutsumi S, Wada W, Yajima T, Kobayahi T, Kubo N and Kuwano H: E/N-cadherin switch mediates cancer progression via TGF-β-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma. Br J Cancer. 105:1885–1893. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Huang J, Xiao D, Li G, Ma J, Chen P, Yuan W, Hou F, Ge J, Zhong M, Tang Y, et al: EphA2 promotes epithelial-mesenchymal transition through the Wnt/β-catenin pathway in gastric cancer cells. Oncogene. 33:2737–2747. 2014. View Article : Google Scholar

28 

Liu Z, Chen L, Zhang X, Xu X, Xing H, Zhang Y, Li W, Yu H, Zeng J and Jia J: RUNX3 regulates vimentin expression via miR-30a during epithelial-mesenchymal transition in gastric cancer cells. J Cell Mol Med. 18:610–623. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Ennen M, Klotz R, Touche N, Pinel S, Barbieux C, Besancenot V, Brunner E, Thiebaut D, Jung AC, Ledrappier S, et al: DDB2: A novel regulator of NF-κB and breast tumor invasion. Cancer Res. 73:5040–5052. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Wu K, Zeng J, Li L, Fan J, Zhang D, Xue Y, Zhu G, Yang L, Wang X and He D: Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors. Oncol Rep. 23:1545–1552. 2010.PubMed/NCBI

31 

Chua HL, Bhat-Nakshatri P, Clare SE, Morimiya A, Badve S and Nakshatri H: NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: Potential involvement of ZEB-1 and ZEB-2. Oncogene. 26:711–724. 2007. View Article : Google Scholar

32 

Min C, Eddy SF, Sherr DH and Sonenshein GE: NF-kappaB and epithelial to mesenchymal transition of cancer. J Cell Biochem. 104:733–744. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

November 2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Cho, I., Jang, E.H., Hong, D., Jung, B., Park, M., & Kim, J. (2015). Suppression of LPS-induced epithelial-mesenchymal transition by aqueous extracts of Prunella vulgaris through inhibition of the NF-κB/Snail signaling pathway and regulation of EMT-related protein expression. Oncology Reports, 34, 2445-2450. https://doi.org/10.3892/or.2015.4218
MLA
Cho, I., Jang, E. H., Hong, D., Jung, B., Park, M., Kim, J."Suppression of LPS-induced epithelial-mesenchymal transition by aqueous extracts of Prunella vulgaris through inhibition of the NF-κB/Snail signaling pathway and regulation of EMT-related protein expression". Oncology Reports 34.5 (2015): 2445-2450.
Chicago
Cho, I., Jang, E. H., Hong, D., Jung, B., Park, M., Kim, J."Suppression of LPS-induced epithelial-mesenchymal transition by aqueous extracts of Prunella vulgaris through inhibition of the NF-κB/Snail signaling pathway and regulation of EMT-related protein expression". Oncology Reports 34, no. 5 (2015): 2445-2450. https://doi.org/10.3892/or.2015.4218