Heterophyllin B inhibits the adhesion and invasion of ECA‑109 human esophageal carcinoma cells by targeting PI3K/AKT/β‑catenin signaling

Tantai,Ji‑Cheng; Zhang,Yao; Zhao,Heng

doi:10.3892/mmr.2015.4659

Heterophyllin B inhibits the adhesion and invasion of ECA‑109 human esophageal carcinoma cells by targeting PI3K/AKT/β‑catenin signaling

Authors:
- Ji‑Cheng Tantai
- Yao Zhang
- Heng Zhao
View Affiliations

Affiliations: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China, Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, P.R. China
Published online on: December 8, 2015 https://doi.org/10.3892/mmr.2015.4659
Pages: 1097-1104
Copyright: © Tantai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to measure the effect of heterophyllin B (HB) on the adhesion and invasion of ECA‑109 human esophageal carcinoma cells, and examine the possible mechanism involved. A Cell Counting kit 8 assay was performed to determine the cell viability. Cell adhesion and invasion were determined following treatment of the ECA‑109 cells with HB (0, 10, 25 and 50 µM) for 24 h. The levels of phosphorylated (p‑)ATK and p‑phosphoinositide 3‑kinase (PI3K), and the protein levels of β‑catenin were measured using western blot analysis. The mRNA and protein expression levels of E‑cadherin, vimentin, snail, matrix metalloproteinase (MMP)2 and MMP9 were detected using reverse trancsription‑quantitative polymerase chain reaction and western blot analyses, respectively. HB (10, 25 and 50 µM) significantly suppressed the adhesion and invasion of the ECA‑109 human esophageal carcinoma cells in a dose‑dependant manner. The expression levels of p‑ATK, p‑PI3K and β‑catenin were markedly decreased. The expression of E‑cadherin was promoted, whereas the expression levels of snail, vimentin, MMP 2 and MMP 9 were decreased significantly in the ECA‑109 cells treated with HB. In addition, HB inhibited the adhesion and invasion induced by PI3K activating peptide in the ECA‑109 cells, and the protein expression levels were also adjusted. These results suggested that HB effectively suppressed the adhesion and invasion of the human esophageal carcinoma cells by mediating the PI3K/AKT/β‑catenin pathways and regulating the expression levels of adhesion‑ and invasion‑associated genes.

View Figures

View References

1	Zhang L, Sun J, Zhang JQ, Yang M, Bai G and Ma XL: Expression and significance of molecular biomarkers in esophageal carcinoma in different nationalities patients in Xinjiang. Genet Mol Res. 13:5413–5425. 2014. View Article : Google Scholar : PubMed/NCBI
2	Shin D, Protano MA, Polydorides AD, Dawsey SM, Pierce MC, Kim MK, Schwarz RA, Quang T, Parikh N, Bhutani MS, et al: Quantitative analysis of high-resolution microendoscopic images for diagnosis of esophageal squamous cell carcinoma. Clin Gastroenterol Hepatol. 13:272–279.e2. 2015. View Article : Google Scholar
3	Dey B, Raphael V, Khonglah Y and Lynrah KG: Immunohistochemical analysis of P53 and PRB in esophageal squamous cell carcinoma. J Clin Diagn Res. 8:FC01–FC03. 2014.PubMed/NCBI
4	Daly JM, Fry WA, Little AG, Winchester DP, McKee RF, Stewart AK and Fremgen AM: Esophageal cancer: Results of an American College of Surgeons patient care evaluation study. J Am Coll Surg. 190:562–573. 2000. View Article : Google Scholar : PubMed/NCBI
5	Schneider T, Müller A, Miess H and Gross H: Cyclic lipopeptides as antibacterial agents-potent antibiotic activity mediated by intriguing mode of actions. Int J Med Microbiol. 304:37–43. 2014. View Article : Google Scholar
6	Farace G, Fernandez O, Jacquens L, Coutte F, Krier F, Jacques P, Clément C, Barka EA, Jacquard C and Dorey S: Cyclic lipopeptides from Bacillus subtilis activate distinct patterns of defence responses in grapevine. Mol Plant Pathol. 16:177–187. 2014. View Article : Google Scholar : PubMed/NCBI
7	Zhang DJ, Liu RF, Li YG, Tao LM and Tian L: Two new anti-fungal cyclic lipopeptides from Bacillus marinus B-9987. Chem Pharm Bull (Tokyo). 58:1630–1634. 2010. View Article : Google Scholar
8	Zhao WO, Pang L, Dong N and Yang S: LC-ESI-MS/MS analysis and pharmacokinetics of heterophyllin B, a cyclic octapeptide from Pseudostellaria heterophylla in rat plasma. Biomed Chromatogr. May 12–2015.epub ahead of print. View Article : Google Scholar
9	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2[-Delta DeltaC(T)] method. Methods. 25:402–408. 2001. View Article : Google Scholar
10	Ye ZY, Deng H, Jian MX, Zheng S and Tian HQ: Anther development and sperm isolation of Pseudostellaria heterophylla (Miq.). Fen Zi Xi Bao Sheng Wu Xue Bao. 40:428–436. 2007.In Chinese.
11	Wang HX and Ng TB: Concurrent isolation of a Kunitz-type trypsin inhibitor with antifungal activity and a novel lectin from Pseudostellaria heterophylla roots. Biochem Biophys Res Commun. 342:349–353. 2006. View Article : Google Scholar : PubMed/NCBI
12	Xu M, Qian G, Xie F, Shi C, Yan L, Yu L, Zheng T, Wei L and Yang J: Expression of epithelial cell adhesion molecule associated with elevated ductular reactions in hepatocellar carcinoma. Clin Res Hepatol Gastroenterol. 38:699–705. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yamada S, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Arakawa Y, Kanamoto M, Iwahashi S, Saito Y, Takasu C, et al: Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy. Ann Surg Oncol. 21(Suppl 3): S436–S442. 2014. View Article : Google Scholar : PubMed/NCBI
14	Sabine VS, Crozier C, Brookes CL, Drake C, Piper T, van de Velde CJ, Hasenburg A, Kieback DG, Markopoulos C, Dirix L, et al: Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study. J Clin Oncol. 32:2951–2958. 2014. View Article : Google Scholar : PubMed/NCBI
15	Toulany M, Minjgee M, Saki M, Holler M, Meier F, Eicheler W and Rodemann HP: ERK2-dependent reactivation of Akt mediates the limited response of tumor cells with constitutive K-RAS activity to PI3K inhibition. Cancer Biol Ther. 15:317–328. 2014. View Article : Google Scholar :
16	Yang Y, Yang JJ, Tao H and Jin WS: New perspectives on β-catenin control of cell fate and proliferation in colon cancer. Food Chem Toxicol. 74:14–19. 2014. View Article : Google Scholar : PubMed/NCBI
17	Nakagawa Y, Ohira M, Kubo N, Yamashita Y, Sakurai K, Toyokawa T, Tanaka H, Muguruma K, Shibutani M, Yamazoe S, et al: Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma. Anticancer Res. 33:5023–5029. 2013.PubMed/NCBI
18	Ivaska J, Pallari HM, Nevo J and Eriksson JE: Novel functions of vimentin in cell adhesion, migration and signaling. Exp Cell Res. 313:2050–2062. 2007. View Article : Google Scholar : PubMed/NCBI
19	Bartoloni E, Alunno A, Bistoni O, Bizzaro N, Migliorini P, Morozzi G, Doria A, Mathieu A, Lotzniker M, Allegri F, et al: Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: An Italian multicentric study and review of the literature. Autoimmun Rev. 11:815–820. 2012. View Article : Google Scholar : PubMed/NCBI
20	Luime JJ, Colin EM, Hazes JM and Lubberts E: Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis. 69:337–344. 2010. View Article : Google Scholar
21	Nieto MA: The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 3:155–166. 2002. View Article : Google Scholar : PubMed/NCBI
22	Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M and Hung MC: Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 6:931–940. 2004. View Article : Google Scholar : PubMed/NCBI
23	Zhang DH, Zhang LY, Liu DJ, Yang F and Zhao JZ: Expression and significance of MMP-9 and MDM2 in the oncogenesis of lung cancer in rats. Asian Pac J Trop Med. 7:585–588. 2014. View Article : Google Scholar : PubMed/NCBI
24	Sun S, Henriksen K, Karsdal MA, Armbrecht G, Belavý DL, Felsenberg D, Rittweger J, Wang Y, Zheng Q and Nedergaard AF: Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy. Exp Gerontol. 58:83–89. 2014. View Article : Google Scholar : PubMed/NCBI
25	Chen L, Zhou Q, Xu B, Liu J, Shi L, Zhu D, Wu C and Jiang J: MT2-MMP expression associates with tumor progression and angiogenesis in human lung cancer. Int J Clin Exp Pathol. 7:3469–3477. 2014.PubMed/NCBI
26	Barber CJ, Pujara PT, Reed DW, Chiwocha S, Zhang H and Covello PS: The two-step biosynthesis of cyclic peptides from linear precursors in a member of the plant family Caryophyllaceae involves cyclization by a serine protease-like enzyme. J Biol Chem. 288:12500–12510. 2013. View Article : Google Scholar : PubMed/NCBI
27	Monroc S, Badosa E, Feliu L, Planas M, Montesinos E and Bardaji E: De novo designed cyclic cationic peptides as inhibitors of plant pathogenic bacteria. Peptides. 27:2567–2574. 2006. View Article : Google Scholar : PubMed/NCBI
28	Xu J and Wu CL: Anti-metastasis of celastrol on esophageal cancer cells and its mechanism. Sheng Li Xue Bao. 67:341–347. 2015.PubMed/NCBI
29	Perlikos F, Harrington KJ and Syrigos KN: Key molecular mechanisms in lung cancer invasion and metastasis: A comprehensive review. Crit Rev Oncol Hematol. 87:1–11. 2013. View Article : Google Scholar : PubMed/NCBI
30	Gimona M and Buccione R: Adhesions that mediate invasion. Int J Biochem Cell Biol. 38:1875–1892. 2006. View Article : Google Scholar : PubMed/NCBI
31	Zhang B, Yin C, Li H, Shi L, Liu N, Sun Y, Lu S, Liu Y, Sun L, Li X, et al: Nir1 promotes invasion of breast cancer cells by binding to chemokine (C–C motif) ligand 18 through the PI3K/Akt/GSK3β/Snail signalling pathway. Eur J Cancer. 49:3900–3913. 2013. View Article : Google Scholar : PubMed/NCBI
32	Xu M, Huang H, Xiong Y, Peng B, Zhou Z, Wang D and Yang X: Combined chemotherapy plus endostar with sequential stereotactic radiotherapy as salvage treatment for recurrent esophageal cancer with severe dyspnea: A case report and review of the literature. Oncol Lett. 8:291–294. 2014.PubMed/NCBI
33	Polivka J Jr and Janku F: Molecular targets for cancer therapy in the PI3K/AKT/mTOR athway. Pharmacol Ther. 142:164–175. 2014. View Article : Google Scholar
34	Yang LH, Xu HT, Han Y, Li QC, Liu Y, Zhao Y, Yang ZQ, Dong QZ, Miao Y, Dai SD, et al: Axin downregulates TCF-4 transcription via β-catenin, but not p53, and inhibits the proliferation and invasion of lung cancer cells. Mol Cancer. 9(25)2010. View Article : Google Scholar
35	Colas E, Pedrola N, Devis L, Ertekin T, Campoy I, Martínez E, Llauradó M, Rigau M, Olivan M, Garcia M, et al: The EMT signaling pathways in endometrial carcinoma. Clin Transl Oncol. 14:715–720. 2012. View Article : Google Scholar : PubMed/NCBI
36	Gao D, Vahdat LT, Wong S, Chang JC and Mittal V: Microenvironmental regulation of epithelial-mesenchymal transitions in cancer. Cancer Res. 72:4883–4889. 2012. View Article : Google Scholar : PubMed/NCBI
37	Cai J: Roles of transcriptional factor Snail and adhesion factor E-cadherin in clear cell renal cell carcinoma. Exp Ther Med. 6:1489–1493. 2013.PubMed/NCBI
38	Cheng JC, Chang HM and Leung PC: Transforming growth factor-β1 inhibits trophoblast cell invasion by inducing Snail-mediated down-regulation of vascular endothelial-cadherin protein. J Biol Chem. 288:33181–33192. 2013. View Article : Google Scholar : PubMed/NCBI
39	Hao L, Ha JR, Kuzel P, Garcia E and Persad S: Cadherin switch from E- to N-cadherin in melanoma progression is regulated by the PI3K/PTEN pathway through Twist and Snail. Br J Dermatol. 166:1184–1197. 2012. View Article : Google Scholar : PubMed/NCBI
40	Zhu Y, Xu L, Zhang J, Xu W, Liu Y, Yin H, Lv T, An H, Liu L, He H, et al: Klotho suppresses tumor progression via inhibiting PI3K/Akt/GSK3β/Snail signaling in renal cell carcinoma. Cancer Sci. 104:663–671. 2013. View Article : Google Scholar : PubMed/NCBI
41	Jasaitis A, Estevez M, Heysch J, Ladoux B and Dufour S: E-cadherin-dependent stimulation of traction force at focal adhesions via the Src and PI3K signaling pathways. Biophys J. 103:175–184. 2012. View Article : Google Scholar : PubMed/NCBI
42	Radenkovic S, Konjevic G, Jurisic V, Karadzic K, Nikitovic M and Gopcevic K: Values of MMP-2 and MMP-9 in tumor tissue of basal-like breast cancer patients. Cell Biochem Biophys. 68:143–152. 2014. View Article : Google Scholar
43	Chen L, Zhou Q, Xu B, Liu J, Shi L, Zhu D, Wu C and Jiang J: MT2-MMP expression associates with tumor progression and angiogenesis in human lung cancer. Int J Clin Exp Pathol. 7:3469–3477. 2014.PubMed/NCBI
44	Samantaray S, Sharma R, Chattopadhyaya TK, Gupta SD and Ralhan R: Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 130:37–44. 2004. View Article : Google Scholar
45	Li Y, Ma J, Guo Q, Duan F, Tang F, Zheng P, Zhao Z and Lu G: Overexpression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. Dis Esophagus. 22:664–667. 2009. View Article : Google Scholar : PubMed/NCBI
46	Kang MH, Oh SC, Lee HJ, Kang HN, Kim JL, Kim JS and Yoo YA: Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-κB pathway and MMP-9 expression. Exp Cell Res. 317:1746–1762. 2011. View Article : Google Scholar : PubMed/NCBI
47	Yang CQ, Li W, Li SQ, Li J, Li YW, Kong SX, Liu RM, Wang SM and Lv WM: MCP-1 stimulates MMP-9 expression via ERK 1/2 and p38 MAPK signaling pathways in human aortic smooth muscle cells. Cell Physiol Biochem. 34:266–276. 2014. View Article : Google Scholar : PubMed/NCBI