Inhibition of MMP-2 and MMP-9 activities by solvent-partitioned Sargassum horneri extracts

다국어 초록 (Multilingual Abstract)

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content.
Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells.
S. horneri crude extract was fractionated with organic solvents, namely, water (H2O), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solventpartitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting.
Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography.
Except H2O fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2.
Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.

참고문헌 (Reference)

1 Overall CM, "Strategies for MMP inhibition in cancer: innovations for the post-trial era" 2 : 657-672, 2002

2 Plaza M, "Screening for bioactive compounds from algae" 51 : 450-455, 2010

3 de la Mare JA, "Quinones and halogenated monoterpenes of algal origin show antiproliferative effects against breast cancer cells in vitro" 30 : 2187-2200, 2012

4 Tu G, "Progress in the development of matrix metalloproteinase inhibitors" 15 : 1388-1395, 2008

5 Thomas NV, "Potential pharmacological applications of polyphenolic derivatives from marine brown algae" 32 : 325-335, 2011

6 서영완, "Peroxynitrite-scavenging Constituents from the Brown Alga Sargassum thunbergii" 한국생물공학회 9 (9): 212-216, 2004

7 Reuter S, "Oxidative stress, inflammation, and cancer: how are they linked?" 49 : 1603-1616, 2010

8 Patarra RF, "Nutritional value of selected macroalgae" 23 : 205-208, 2011

9 Matanjun P, "Nutrient content of tropical edible seaweeds, Eucheuma cottonii, Caulerpa lentillifera and Sargassum polycystum" 21 : 75-80, 2009

10 Egeblad M, "New functions for the matrix metalloproteinases in cancer progression" 2 : 161-174, 2002

11 Bauvois B, "New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression" 1825 : 29-36, 2012

12 Yin Shipeng, "Measurement of Antioxidant Activities and Phenolic and Flavonoid Contents of the Brown Seaweed Sargassum horneri: Comparison of Supercritical CO2 and Various Solvent Extractions" 한국수산과학회 18 (18): 123-130, 2015

13 Moss LAS, "Matrix metalloproteinases: changing roles in tumor progression and metastasis" 181 : 1895-1899, 2012

14 Kato H, "Matrix metalloproteinase-2 (MMP-2) gene deletion enhances MMP-9 activity, impairs PARP-1 degradation, and exacerbates hepatic ischemia and reperfusion injury in mice" 10 (10): e0137642-, 2015

15 Benjamin MM, "Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease" 103 : 209-279, 2012

16 Bhatnagar I, "Marine antitumor drugs: status, shortfalls and strategies" 8 : 2702-2720, 2010

17 Jiao J, "Hepatic fibrosis" 25 : 223-229, 2009

18 Jones JL, "Control of matrix metalloproteinase activity in cancer" 183 : 377-379, 1997

19 Yu P, "Bioactive substances from marine fishes, shrimps and algae and their functions: present and future" 55 : 1114-1136, 2015

20 Holdt SL, "Bioactive compounds in seaweed: functional food applications and legislation" 23 : 543-597, 2011

21 Ibanez E, "Benefits of using algae as natural sources of functional ingredients" 93 : 703-709, 2013

22 Kim YA, "Anti-inflammatory activity of heterocarpin from the salt marsh plant Corydalis heterocarpa in LPS-induced RAW 264.7 macrophage cells" 20 : 14474-14486, 2015