Evaluation of Effective MMP Inhibitors from Eight Different Brown Algae in Human Fibrosarcoma HT1080 Cells

  • Bae, Min Joo (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Karadeniz, Fatih (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Ahn, Byul-Nim (Department of Organic Material Science and Engineering, Pusan National University) ;
  • Kong, Chang-Suk (Department of Food and Nutrition, College of Medical and Life Science, Silla University)
  • Received : 2015.04.23
  • Accepted : 2015.09.03
  • Published : 2015.09.30


Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.


Supported by : National Research Foundation of Korea (NRF)


  1. Jones JL, Walker RA. 1997. Control of matrix metalloproteinase activity in cancer. J Pathol 183: 377-379.<377::AID-PATH951>3.0.CO;2-R
  2. Shuman Moss LA, Jensen-Taubman S, Stetler-Stevenson WG. 2012. Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am J Pathol 181: 1895-1899.
  3. Egeblad M, Werb Z. 2002. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2: 161-174.
  4. Bauvois B. 2012. New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: Outside-in signaling and relationship to tumor progression. Biochim Biophys Acta 1825: 29-36.
  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.
  6. Ibanez E, Cifuentes A. 2013. Benefits of using algae as natural sources of functional ingredients. J Sci Food Agric 93: 703-709.
  7. Yu P, Gu H. 2015. Bioactive substances from marine fishes, shrimps, and algae and their functions: present and future. Crit Rev Food Sci Nutr 55: 1114-1136.
  8. Patarra RF, Paiva L, Neto AI, Lima E, Baptista J. 2011. Nutritional value of selected macroalgae. J Appl Phycol 23: 205-208.
  9. Matanjun P, Mohamed S, Mustapha NM, Muhammad K. 2009. Nutrient content of tropical edible seaweeds, Eucheuma cottonii, Caulerpa lentillifera and Sargassum polycystum. J Appl Phycol 21: 75-80.
  10. Holdt SL, Kraan S. 2011. Bioactive compounds in seaweed: functional food applications and legislation. J Appl Phycol 23: 543-597.
  11. Plaza M, Santoyo S, Jaime L, Garcia-Blairsy Reina G, Herrero M, Senorans FJ, Ibanez E. 2010. Screening for bioactive compounds from algae. J Pharm Biomed Anal 51: 450-455.
  12. Thomas NV, Kim SK. 2011. Potential pharmacological applications of polyphenolic derivatives from marine brown algae. Environ Toxicol Pharmacol 32: 325-335.
  13. de la Mare JA, Lawson JC, Chiwakata MT, Beukes DR, Edkins AL, Blatch GL. 2012. Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro. Invest New Drugs 30: 2187-2200.
  14. Jiao J, Friedman SL, Aloman C. 2009. Hepatic fibrosis. Curr Opin Gastroenterol 25: 223-229.
  15. 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.
  16. Bhatnagar I, Kim SK. 2010. Marine antitumor drugs: status, shortfalls and strategies. Mar Drugs 8: 2702-2720.
  17. Tu G, Xu W, Huang H, Li S. 2008. Progress in the development of matrix metalloproteinase inhibitors. Curr Med Chem 15: 1388-1395.
  18. Jiao G, Yu G, Zhang J, Ewart HS. 2011. Chemical structures and bioactivities of sulfated polysaccharides from marine algae. Mar Drugs 9: 196-223.
  19. Nguyen VT, Qian ZJ, Lee B, Heo SJ, Kim KN, Jeon YJ, Park WS, Choi IW, Jang CH, Ko SC, Park SJ, Kim YT, Kim GH, Lee DS, Yim MJ, Je JY, Jung WK. 2014. Fucoxanthin derivatives from Sargassum siliquastrum inhibit matrix metalloproteinases by suppressing NF-${\kappa}B$ and MAPKs in human fibrosarcoma cells. ALGAE 29: 355-366.
  20. Kim MM, Rajapakse N, Kim SK. 2009. Anti-inflammatory effect of Ishige okamurae ethanolic extract via inhibition of NF-${\kappa}B$ transcription factor in RAW 264.7 cells. Phytother Res 23: 628-634.
  21. 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.
  22. Bourboulia D, Stetler-Stevenson WG. 2010. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Semin Cancer Biol 20: 161-168.
  23. Zhang C, Kim SK. 2009. Matrix metalloproteinase inhibitors (MMPIs) from marine natural products: the current situation and future prospects. Mar Drugs 7: 71-84.

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