3,5-Dicaffeoyl-epi-quinic acid inhibits the PMA-stimulated activation and expression of MMP-9 but not MMP-2 via downregulation of MAPK pathway
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Jung Im Lee
Abstract
Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are very important gelatinases that are overexpressed during tumor metastasis. Up to date, several MMP inhibitors have been developed from natural sources as well as organic synthesis. In the present study, the MMP-2 and MMP-9 inhibitory effects of 3,5-dicaffeoyl-epi-quinic acid (DCEQA), a caffeoylquinic acid derivative isolated from Atriplex gmelinii, were investigated in phorbol 12-myristate 13-acetate (PMA)-treated human HT1080 fibrosarcoma cells. Gelatin zymography and immunoblotting showed that DCEQA significantly inhibited the PMA-induced activation and expression of MMP-9 but was not able to show any effect against MMP-2. DCEQA treatment was also shown to upregulate the protein expression of tissue inhibitor of MMP-1 along with decreased MMP-9 protein levels. Moreover, the effect of DCEQA on phosphorylation of mitogen activated protein kinases (MAPKs), analyzed by immunoblotting, indicated the DCEQA inhibited the MMP-9 by downregulation of MAPK pathway. Collectively, current results suggested that DCEQA is a potent MMP-9 inhibitor and can be utilized as lead compound for treatment of pathological complications involving enhanced MMP activity such as cancer metastasis.
Acknowledgments
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2016R1D1A1B03932769) and by the Ministry of Science and ICT (No. 2019R1F1A1059325).
Disclosure of interest: The authors report no conflict of interest.
References
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34.10.3322/caac.21551Search in Google Scholar PubMed
2. Riggi N, Aguet M, Stamenkovic I. Cancer metastasis: a reappraisal of its underlying mechanisms and their relevance to treatment. Annu Rev Pathol Mech Dis 2018;13:117–40.10.1146/annurev-pathol-020117-044127Search in Google Scholar PubMed
3. Li Y, Rogoff HA, Keates S, Gao Y, Murikipudi S, Mikule K, et al. Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci USA 2015;112:1839–44.10.1073/pnas.1424171112Search in Google Scholar PubMed PubMed Central
4. Kaushik S, Pickup MW, Weaver VM. From transformation to metastasis: deconstructing the extracellular matrix in breast cancer. Cancer Metast Rev 2016;35:655–67.10.1007/s10555-016-9650-0Search in Google Scholar PubMed PubMed Central
5. Guan X. Cancer metastases: challenges and opportunities. Acta Pharm Sin B 2015;5:402–18.10.1016/j.apsb.2015.07.005Search in Google Scholar PubMed PubMed Central
6. Holle AW, Young JL, Spatz JP. In vitro cancer cell–ECM interactions inform in vivo cancer treatment. Adv Drug Deliv Rev 2016;97:270–9.10.1016/j.addr.2015.10.007Search in Google Scholar PubMed
7. Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzym Inhib Med Chem 2016;31:177–83.10.3109/14756366.2016.1161620Search in Google Scholar PubMed
8. Shay G, Lynch CC, Fingleton B. Moving targets: emerging roles for MMPs in cancer progression and metastasis. Matrix Biol 2015;44–46:200–6.10.1016/j.matbio.2015.01.019Search in Google Scholar PubMed PubMed Central
9. Klein G, Vellenga E, Fraaije M, Kamps W, de Bont ESJM. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 2004;50:87–100.10.1016/j.critrevonc.2003.09.001Search in Google Scholar PubMed
10. Li H, Qiu Z, Li F, Wang C. The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncol Lett 2017;14:5865–70.10.3892/ol.2017.6924Search in Google Scholar PubMed PubMed Central
11. Mendes O, Kim H-T, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastas 2005;22:237–46.10.1007/s10585-005-8115-6Search in Google Scholar
12. Kurahara S, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A, et al. Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck 1999;21:627–38.10.1002/(SICI)1097-0347(199910)21:7<627::AID-HED7>3.0.CO;2-2Search in Google Scholar
13. Ejeil A-L, Igondjo-Tchen S, Ghomrasseni S, Pellat B, Godeau G, Gogly B. Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy and diseased human gingiva. J Periodontol 2003;74:188–95.10.1902/jop.2003.74.2.188Search in Google Scholar
14. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002;295:2387–92.10.1126/science.1067100Search in Google Scholar
15. Li J, Lau GK, Chen L, Dong S, Lan H-Y, Huang X-R, et al. Interleukin 17a promotes hepatocellular carcinoma metastasis via nf-kb induced matrix metalloproteinases 2 and 9 expression. PLoS One 2011;6:e21816.10.1371/journal.pone.0021816Search in Google Scholar
16. Lim E-J, Lee S-H, Lee J-G, Kim J-R, Yun S-S, Baek S-H, et al. Toll-like receptor 9 dependent activation of MAPK and nf-kb is required for the CPG ODN-induced matrix metalloproteinase-9 expression. Exp Mol Med 2007;39:239–45.10.1038/emm.2007.27Search in Google Scholar
17. Lin C-C, Tseng H-W, Hsieh H-L, Lee C-W, Wu C-Y, Cheng C-Y, et al. Tumor necrosis factor-α induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-κb in A549 cells. Toxicol Appl Pharmacol 2008;229:386–98.10.1016/j.taap.2008.01.032Search in Google Scholar
18. Chen D-Q, Feng Y-L, Cao G, Zhao Y-Y. Natural products as a source for antifibrosis therapy. Trends Pharmacol Sci 2018;39:937–52.10.1016/j.tips.2018.09.002Search in Google Scholar
19. Hu L, Ying J, Zhang M, Qiu X, Lu Y. Antitumor potential of marine natural products: a mechanistic investigation. Anticancer Agents Med Chem 2018;18:702–18.10.2174/1871520617666170918142811Search in Google Scholar
20. Jiang R-W, Lau K-M, Hon P-M, Mak T, Woo K-S, Fung K-P. Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza. Curr Med Chem 2012;12:237–46.10.2174/0929867053363397Search in Google Scholar
21. Wang H, Provan GJ, Helliwell K. Determination of rosmarinic acid and caffeic acid in aromatic herbs by HPLC. Food Chem 2004;87:307–11.10.1016/j.foodchem.2003.12.029Search in Google Scholar
22. Naveed M, Hejazi V, Abbas M, Kamboh AA, Khan GJ, Shumzaid M, et al. Chlorogenic acid (CGA): a pharmacological review and call for further research. Biomed Pharmacother 2018;97:67–74.10.1016/j.biopha.2017.10.064Search in Google Scholar PubMed
23. Hung TM, Na M, Thuong PT, Su ND, Sok D, Song KS, et al. Antioxidant activity of caffeoyl quinic acid derivatives from the roots of Dipsacus asper wall. J Ethnopharmacol 2006;108:188–92.10.1016/j.jep.2006.04.029Search in Google Scholar PubMed
24. Peng W, Han P, Yu L, Chen Y, Ye B, Qin L, et al. Anti-allergic rhinitis effects of caffeoylquinic acids from the fruits of Xanthium strumarium in rodent animals via alleviating allergic and inflammatory reactions. Rev Bras Farmacogn 2019;29:46–53.10.1016/j.bjp.2018.10.004Search in Google Scholar
25. Xiong J, Li S, Wang W, Hong Y, Tang K, Luo Q. Screening and identification of the antibacterial bioactive compounds from Lonicera japonica Thunb. leaves. Food Chem 2013;138:327–33.10.1016/j.foodchem.2012.10.127Search in Google Scholar PubMed
26. Li Y, But PP, Ooi VE. Antiviral activity and mode of action of caffeoylquinic acids from Schefflera heptaphylla (L.) Frodin. Antiviral Res 2005;68:1–9.10.1016/j.antiviral.2005.06.004Search in Google Scholar PubMed
27. Roleira FMF, Tavares-da-Silva EJ, Varela CL, Costa SC, Silva T, Garrido J, et al. Plant derived and dietary phenolic antioxidants: anticancer properties. Food Chem 2015;183:235–58.10.1016/j.foodchem.2015.03.039Search in Google Scholar PubMed
28. Suzuki I, Hayashi I, Takaki T, Groveman DS, Fujimiya Y. Antitumor and anticytopenic effects of aqueous extracts of propolis in combination with chemotherapeutic agents. Cancer Biother Radiopharm 2002;17:553–62.10.1089/108497802760804781Search in Google Scholar PubMed
29. Oh JH, Lee JI, Karadeniz F, Seo Y, Kong C-S. 3,5-Dicaffeoyl-epi-quinic acid isolated from edible halophyte Atriplex gmelinii inhibits adipogenesis via AMPK/MAPK pathway in 3T3-L1 adipocytes. Evid-Based Compl Alt Med 2018;2018:1–8.10.1155/2018/8572571Search in Google Scholar PubMed PubMed Central
30. Oh J, Karadeniz F, Lee J, Seo Y, Kong C. Protective effect of 3,5-dicaffeoyl-epi-quinic acid against UVB-induced photoaging in human HaCaT keratinocytes. Mol Med Rep 2019;20:763–70.10.3892/mmr.2019.10258Search in Google Scholar PubMed
31. Bae M-J, Karadeniz F, Lee S-G, Seo Y, Kong C-S. Inhibition of MMP-2 and MMP-9 activities by Limonium tetragonum extract. Prev Nutr Food Sci 2016;21:38–43.10.3746/pnf.2016.21.1.38Search in Google Scholar PubMed PubMed Central
32. Malemud CJ. Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci 2006;11:1696.10.2741/1915Search in Google Scholar PubMed
33. Cathcart JM, Cao J. MMP inhibitors: past, present and future. Front Biosci 2015;20:1164–78.10.2741/4365Search in Google Scholar PubMed
34. Mannello F. Natural bio-drugs as matrix metalloproteinase inhibitors: new perspectives on the horizon? Recent Pat Anticancer Drug Discov 2006;1:91–103.10.2174/157489206775246421Search in Google Scholar PubMed
35. Cheng C-Y, Hsieh H-L, Hsiao L-D, Yang C-M. PI3-k/AKT/JNK/Nf-κb is essential for MMP-9 expression and outgrowth in human limbal epithelial cells on intact amniotic membrane. Stem Cell Res 2012;9:9–23.10.1016/j.scr.2012.02.005Search in Google Scholar PubMed
36. Wang T, Jin X, Liao Y, Sun Q, Luo C, Wang G, et al. Association of Nf-κb and AP-1 with MMP-9 overexpression in 2-chloroethanol exposed rat astrocytes. Cells 2018;7:96.10.3390/cells7080096Search in Google Scholar PubMed PubMed Central
37. Yokoyama K, Hiyama A, Arai F, Nukaga T, Sakai D, Mochida J. C-Fos regulation by the MAPK and PKC pathways in intervertebral disc cells. PLoS One 2013;8:e73210.10.1371/journal.pone.0073210Search in Google Scholar PubMed PubMed Central
38. Song G, Xu S, Zhang H, Wang Y, Xiao C, Jiang T, et al. TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3k/AKT and MAPK pathway. J Exp Clin Cancer Res 2016;35:148.10.1186/s13046-016-0427-7Search in Google Scholar PubMed PubMed Central
39. Ordoñez R, Carbajo-Pescador S, Prieto-Dominguez N, García-Palomo A, González-Gallego J, Mauriz JL. Inhibition of matrix metalloproteinase-9 and nuclear factor kappa b contribute to melatonin prevention of motility and invasiveness in HepG2 liver cancer cells. J Pineal Res 2014;56:20–30.10.1111/jpi.12092Search in Google Scholar PubMed
40. Chiao YA, Dai Q, Zhang J, Lin J, Lopez EF, Ahuja SS, et al. Multi-analyte profiling reveals matrix metalloproteinase-9 and monocyte chemotactic protein-1 as plasma biomarkers of cardiac aging. Circ Cardiovasc Genet 2011;4:455–62.10.1161/CIRCGENETICS.111.959981Search in Google Scholar PubMed PubMed Central
41. Yang C-Q, Li W, Li S-Q, Li J, Li Y-W, Kong S-X, et al. MCP-1 stimulates MMP-9 expression via ERK 1/2 and p38 MAPK signaling pathways in human aortic smooth muscle cells. Cell Physiol Biochem 2014;34:266–76.10.1159/000362997Search in Google Scholar PubMed
42. Yamamoto T, Eckes B, Mauch C, Hartmann K, Krieg T. Monocyte chemoattractant protein-1 enhances gene expression and synthesis of matrix metalloproteinase-1 in human fibroblasts by an autocrine IL-1 loop. J Immunol 2000;164:6174–9.10.4049/jimmunol.164.12.6174Search in Google Scholar PubMed
©2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Research Articles
- Polyphenol content and bioactivity of Achillea moschata from the Italian and Swiss Alps
- Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells
- Identification of tuliposide G, a novel glucoside ester-type tuliposide, and its distribution in tulip
- Activity-guided isolation of cholinesterase inhibitors quercetin, rutin and kaempferol from Prunus persica fruit
- Letter to the editor
- HIV-1 Tat protein potentiated ABCC-mediated efflux in Jurkat cells
- Research Articles
- A possible alternative therapy for type 2 diabetes using Myristica fragrans Houtt in combination with glimepiride: in vivo evaluation and in silico support
- 3,5-Dicaffeoyl-epi-quinic acid inhibits the PMA-stimulated activation and expression of MMP-9 but not MMP-2 via downregulation of MAPK pathway
- Enzyme inhibitory assessment of the isolated constituents from Plantago holosteum Scop.
Articles in the same Issue
- Frontmatter
- Research Articles
- Polyphenol content and bioactivity of Achillea moschata from the Italian and Swiss Alps
- Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells
- Identification of tuliposide G, a novel glucoside ester-type tuliposide, and its distribution in tulip
- Activity-guided isolation of cholinesterase inhibitors quercetin, rutin and kaempferol from Prunus persica fruit
- Letter to the editor
- HIV-1 Tat protein potentiated ABCC-mediated efflux in Jurkat cells
- Research Articles
- A possible alternative therapy for type 2 diabetes using Myristica fragrans Houtt in combination with glimepiride: in vivo evaluation and in silico support
- 3,5-Dicaffeoyl-epi-quinic acid inhibits the PMA-stimulated activation and expression of MMP-9 but not MMP-2 via downregulation of MAPK pathway
- Enzyme inhibitory assessment of the isolated constituents from Plantago holosteum Scop.