- Volume 21 Issue 1
DOI QR Code
Inhibition of MMP-2 and MMP-9 Activities by Limonium tetragonum Extract
- Bae, Min-Joo (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University) ;
- Karadeniz, Fatih (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University) ;
- Lee, Seul-Gi (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University) ;
- Seo, Youngwan (Department of Convergence Study on the Ocean Science and Technology, Ocean Science and Technology School, College of Ocean Science and Technology, Korea Maritime and Ocean University) ;
- Kong, Chang-Suk (Department of Food and Nutrition, College of Medical and Life Sciences, Silla University)
- Received : 2016.01.04
- Accepted : 2016.02.17
- Published : 2016.03.31
Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that take important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Natural products are on the rise for their potential to provide remarkable health benefits. In this context, halophytes have been of interest in the nutraceutical field with reported instances of isolation of bioactive compounds. In this study, Limonium tetragonum, an edible halophyte, was studied for its ability to inhibit MMP-2 and -9 using HT1080 fibrosarcoma cells. Results showed that L. tetragonum extract was able to inhibit the enzymatic activity and mRNA expression of MMP-2 and -9 according to gelatin zymography and RT-PCR assays, respectively, but it was not able to significantly change the MMP pathway related factors such as tissue inhibitors of metalloproteinases. Also, Mitogen-activated protein kinases pathway-related protein levels and their phosphorylation were assayed. While the phosphorylated p38 levels were decreased, extracellular signal-regulated kinase and c-Jun N-terminal kinase were not affected by L. tetragonum treatment. In conclusion, it was suggested that L. tetragonum contains substances acting as MMP inhibitors on enzymatic activity rather than intracellular pathway intervention, which could be useful for further utilization of L. tetragonum as a source for anti-MMP agents.
Supported by : National Research Foundation of Korea (NRF)
- da Rocha AB, Lopes RM, Schwartsmann G. 2001. Natural products in anticancer therapy. Curr Opin Pharmacol 1: 364-369. https://doi.org/10.1016/S1471-4892(01)00063-7
- Kim YA, Kong CS, Lee JI, Kim H, Park HY, Lee HS, Lee C, Seo Y. 2012. Evaluation of novel antioxidant triterpenoid saponins from the halophyte Salicornia herbacea. Bioorg Med Chem Lett 22: 4318-4322. https://doi.org/10.1016/j.bmcl.2012.05.017
- Ksouri R, Smaoui A, Isoda H, Abdelly C. 2012. Utilization of halophyte species as new sources of bioactive substances. J Arid Land Stud 22: 41-44.
- Lee JI, Kong CS, Jung ME, Hong JW, Noh I, Seo Y. 2011. Peroxynitrite-scavenging activity of the halophyte Limonium tetragonum. Ocean Polar Res 33: 185-191. https://doi.org/10.4217/OPR.2011.33.2.185
- Yang MH, Kim NH, Heo JD, Sung SH, Jeong EJ. 2014. Hepatoprotective effects of Limonium tetragonum, edible medicinal halophyte growing near seashores. Pharmacogn Mag 10: 563-568. https://doi.org/10.4103/0973-1296.139783
- Lee JI, Kong CS, Jung ME, Hong JW, Lim SY, Seo Y. 2011. Antioxidant activity of the halophyte Limonium tetragonum and its major active components. Biotechnol Bioprocess Eng 16: 992-999. https://doi.org/10.1007/s12257-011-0213-5
- Overall CM, Lopez-Otin C. 2002. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2: 657-672. https://doi.org/10.1038/nrc884
- Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K, Takano Y. 2006. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26: 3579-3583.
- Kong CS, Um YR, Lee JI, Kim YA, Yea SS, Seo Y. 2010. Constituents isolated from Glehnia littoralis suppress proliferations of human cancer cells and MMP expression in HT1080 cells. Food Chem 120: 385-394. https://doi.org/10.1016/j.foodchem.2009.09.096
- Kong CS, Kim YA, Kim MM, Park JS, Kim JA, Kim SK, Lee BJ, Nam TJ, Seo Y. 2008. Flavonoid glycosides isolated from Salicornia herbacea inhibit matrix metalloproteinase in HT1080 cells. Toxicol In Vitro 22: 1742-1748. https://doi.org/10.1016/j.tiv.2008.07.013
- Jiao J, Friedman SL, Aloman C. 2009. Hepatic fibrosis. Curr Opin Gastroenterol 25: 223-229. https://doi.org/10.1097/MOG.0b013e3283279668
- Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. 2010. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic Biol Med 49: 1603-1616. https://doi.org/10.1016/j.freeradbiomed.2010.09.006
- Bhatnagar I, Kim SK. 2010. Marine antitumor drugs: status, shortfalls and strategies. Mar Drugs 8: 2702-2720. https://doi.org/10.3390/md8102702
- Tu G, Xu W, Huang H, Li S. 2008. Progress in the development of matrix metalloproteinase inhibitors. Curr Med Chem 15: 1388-1395. https://doi.org/10.2174/092986708784567680
- Brew K, Nagase H. 2010. The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity. Biochim Biophys Acta 1803: 55-71. https://doi.org/10.1016/j.bbamcr.2010.01.003
- Bourboulia D, Stetler-Stevenson WG. 2010. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Seminars Cancer Biol 20: 161-168. https://doi.org/10.1016/j.semcancer.2010.05.002
- Davidson B, Givant-Horwitz V, Lazarovici P, Risberg B, Nesland JM, Trope CG, Schaefer E, Reich R. 2003. Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): co-expression in metastatic serous ovarian carcinoma. Clin Exp Metastasis 20: 621-631. https://doi.org/10.1023/A:1027347932543
- Reddy KB, Krueger JS, Kondapaka SB, Diglio CA. 1999. Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int J Cancer 82: 268-273. https://doi.org/10.1002/(SICI)1097-0215(19990719)82:2<268::AID-IJC18>3.0.CO;2-4
Kim ES, Kim MS, Moon A. 2004. TGF-
$\beta$-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. Int J Oncol 25: 1375-1382.
- Vijayababu MR, Arunkumar A, Kanagaraj P, Venkataraman P, Krishnamoorthy G, Arunakaran J. 2006. Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3). Mol Cell Biochem 287: 109-116. https://doi.org/10.1007/s11010-005-9085-3
- Ende C, Gebhardt R. 2004. Inhibition of matrix metalloproteinase-2 and -9 activities by selected flavonoids. Planta Med 70: 1006-1008. https://doi.org/10.1055/s-2004-832630
- Kim NH, Sung SH, Heo JD, Jeong EJ. 2015. The extract of Limonium tetragonum protected liver against acute alcohol toxicity by enhancing ethanol metabolism and antioxidant enzyme activities. Nat Prod Sci 21: 54-58.
- ZFP403, a novel tumor suppressor, inhibits the proliferation and metastasis in ovarian cancer 2017, https://doi.org/10.1016/j.ygyno.2017.08.025
- MMP-Inhibitory Effects of Flavonoid Glycosides from Edible Medicinal Halophyte Limonium tetragonum vol.2017, 2017, https://doi.org/10.1155/2017/6750274
- Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/−9 and heparanase in MDA-MB-231 cells vol.37, pp.1, 2017, https://doi.org/10.3892/or.2016.5269
- Evaluation of MMP Inhibitors Isolated from Ligustrum japonicum Fructus vol.24, pp.3, 2019, https://doi.org/10.3390/molecules24030604