Browse > Article
http://dx.doi.org/10.5352/JLS.2016.26.6.673

Aesculetin Inhibits Cell Invasion through Inhibition of MMP-9 Activity and Antioxidant Activity  

Hong, Sugyeong (Department of Chemistry, Dong-Eui University)
Kim, Moon-Moo (Department of Chemistry, Dong-Eui University)
Publication Information
Journal of Life Science / v.26, no.6, 2016 , pp. 673-679 More about this Journal
Abstract
The development of safe and effective anti-cancer compounds has been seriously required to prevent and treat development of tumor in recent years. Among them, natural compounds derived traditional medicinal stuffs have been paid to attention as an anti-cancer candidate. In this study, aesculetin is a main component of a widely known as a medicinal stuff. It was reported that aesculetin has various biological effects such as anti-inflammatory and anti-bacterial, but its effect related to cell invasion was not discovered. Therefore, in this study, the effect of aesculetin on antioxidant and matrix metalloproteases (MMPs) was investigated in human fibrosarcoma cells, HT1080. First of all, aesculetin showed the scavenging activity of DPPH radical and reducing power in a dose dependent manner. As a result of cytotoxicity, the nontoxic concentration of aesculetin was below 2 μM in HT1080 cells performed by MTT assay. In addition, aesculetin displayed the inhibitory effect on MMP-9 activity related to cell invasion in experiment carried out by gelatin zymography assay. Furthermore, aesculetin increased the expression level of TIMP-1 but decreased the expression level of MMP-9 stimulated with PMA in western blot assay. Furthermore, aesculetin remarkably inhibited cell invasion related to metastasis a dose dependent manner. Above results suggest that aesculetin could exert chemopreventive effect through inhibition of activity and expression of MMP-9 related to cell invasion.
Keywords
Aesculetin; antioxidant; MMP-9; TIMP-1; cell invasion;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Cao, L. H., Lee, Y. J., Kang, D. G., Kim, J. S. and Lee, H. S. 2009. Effect of Zanthoxylum schinifolium on TNF-α-induced vascular inflammation in human umbilical vein endothelial cells. Vascul. Pharmacol. 50, 200-207.   DOI
2 Choi, H. J., Chung, T. W., Kim, J. E., Jeong, H. S., Joo, M. s., Cha, J. h., Kim, C. H. and Ha, K. T. 2012. Aesculin inhibits matrix metalloproteinase-9 expression via p38 mitogen activated protein kinase and activator protein 1 in lipopolysachride-induced RAW264. 7 cells. Int. Immunopharmacol. 14, 267-274.   DOI
3 Choi, S. I., Chang, K. M., Lee, Y. S. and Kim, G. H. 2008. Antibacterial activity of essential oils from Zanthoxylum piperitum AP DC. and Zanthoxylum schinifolium. Food Sci. Biotechnol. 17, 195-198.
4 Egeblad, M. and Werb, Z. 2002. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161-174.   DOI
5 D’Autréaux, B. and Toledano, M. B. 2007. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol. 8, 813-824.
6 Groblewska, M., Siewko, M., Mroczko, B. and Szmitkowski, M. 2012. The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer. Folia Histochem. Cytobiol. 50, 12-19.   DOI
7 Han, W. and Wang, M. H. 2010. Radical scavenging and anti-inflammation activities from different extracts of zanthoxylum schnifolium Fruits. Kor. J. Pharmacognosy 41, 250-254.
8 Hansen, M. B., Nielsen, S. E. and Berg, K. 1989. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods 119, 203-210.   DOI
9 Hua, H., Li, M., Luo, T., Yin, Y. and Jiang, Y. 2011. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell. Mol. Life Sci. 68, 3853-3868.   DOI
10 Imai, J., Ide, N., Nagae, S., Moriguchi, T., Matsuura, H. and Itakura, Y. 1994. Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 60, 417-420.   DOI
11 Kim, K. W., Kim, J. S. and Baek, J. K. 2005. Isolation of herbicidal compounds from the fruit of zanthoxylum schinifolium S. et. Z. Kor. J. Weed Sci. 3, 194-201.
12 Lee, S. Y., Lim, T. G., Chen, H., Jung, S. K., Lee, H. J., Lee, M. H., Kim, D. J., Shin, A., Lee, K. W. and Bode, A. M. 2013. Esculetin suppresses proliferation of human colon cancer cells by directly targeting β-catenin. Cancer Prev. Res. 6, 1356-1364.   DOI
13 John, A. and Tuszynski, G. 2001. The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol. Oncol. Res. 7, 14-23.   DOI
14 Khan, N. and Mukhtar, H. 2010. Cancer and metastasis: prevention and treatment by green tea. Cancer Metastasis Rev. 29, 435-445.   DOI
15 Leutner, S., Eckert, A. and Müller, W. 2001. ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J. Neural. Transm. 108, 955-967.   DOI
16 Moss, L. A. S., Jensen-Taubman, S. and Stetler-Stevenson, W. G. 2012. Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am. J. Pathol. 181, 1895-1899.   DOI
17 No, Y. D., Sin, M. G. and Song, H. J. 1997. A herbalogical study on the plants of rutaceae grown in Korea. Kor. J. Herbology 12, 135-135.
18 Oyaizu, M. 1986. Studies on products of browning reaction--antioxidative activities of products of browning reaction prepared from glucosamine. Jpn. J. Nut. 44, 307-315.   DOI
19 Park, S. L., Won, S. Y., Song, J. H., Lee, S. Y., Kim, W. J. and Moon, S. K. 2016. Esculetin inhibits VEGF-induced angiogenesis both in vitro and in vivo. Am. J. Chin. Med. 44, 61-76.
20 Sosa, V., Moliné, T., Somoza, R., Paciucci, R., Kondoh, H. and LLeonart, M. E. 2013. Oxidative stress and cancer: an overview. Ageing Res. Rev. 12, 376-390.   DOI
21 Thuong, P. T., Hung, T. M., Ngoc, T. M., Ha, D. T., Min, B. S., Kwack, S. J., Kang, T. S., Choi, J. S. and Bae, K. 2010. Antioxidant activities of coumarins from Korean medicinal plants and their structure–activity relationships. Phytother. Res. 24, 101-106.   DOI
22 Valko, M., Rhodes, C., Moncol, J., Izakovic, M. and Mazur, M. 2006. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 160, 1-40.   DOI
23 Bhattacharya, S. 2015.Reactive Oxygen Species and Cellular Defense System.17-29. Free Radicals in Human Health and Disease: Springer.
24 Cheng, M. J., Yang, C. H., Lin, W. Y., Lin, W. Y., Tsai, I. L. and Chen, I. S. 2002. Chemical constituents from the leaves of Zanthoxylum schinifolium. J. Chin. Chem. Soc. 49, 125-128.   DOI
25 Aroui, S., Najlaoui, F., Chtourou, Y., Meunier, A. C., Laajimi, A., Kenani, A. and Fetoui, H. 2015. Naringin inhibits the invasion and migration of human glioblastoma cell via downregulation of MMP-2 and MMP-9 expression and inactivation of p38 signaling pathway. Tumour Biol. 37, 3831-3839.