Lee, Seul-Gi
(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)
,
Oh, Jung Hwan
(Department of Food and Nutrition, College of Medical and Life Sciences, Silla University)
,
Yu, Ga Hyun
(Department of Food and Nutrition, College of Medical and Life Sciences, Silla University)
,
Kong, Chang-Suk
(Department of Food and Nutrition, College of Medical and Life Sciences, Silla University)
Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to posse...
Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, $H_2O$, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the $H_2O$ fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts.
Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, $H_2O$, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the $H_2O$ fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts.
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제안 방법
First, HFEs were tested for their cytotoxic presence in the human fibrosarcoma cell line HT1080 for 48 h at two different concentrations (5 and 50 μg/mL) (Fig. 1).
The target cDNA was amplified using the following primers: forward 5’-TGA-AGG-TCG-GTG-TGA-ACG-GA-3’ and reverse 5’-CAT-GTA-GCC-ATG-AGG-TCC-ACC-AC-3’ for MMP-2; forward 5’-CAC-TGT-CCA-CCC-CTC-AGAGC-3’ and reverse 5’-CAC-TTG-TCG-GCG-ATA-AGG-3’ for MMP-9; forward 5’-AAT-TCC-GAC-CTC-GTC-ATCAG-3’ and reverse 5’-TGC-AGT-TTT-CCA-GCA-ATGAG-3’ for TIMP-1; forward 5’-TGA-TCC-ACA-CAC-GTTGGT-CT-3’ and reverse 5’-TTT-GAG-TTG-CTT-GCAGGA-TG-3’ for TIMP-2; forward 5’-GCC-ACC-CAG-AAGACT-GTG-GAT-3’ and reverse 5’-TGG-TCC-AGG-GTTTCT-TAC-TCC-3’ for β-actin.
데이터처리
Differences between the calculated means of the each individual group were determined by one-way ANOVA coupled with Duncan’s multiple range tests.
Means with the different letters are significantly different (P<0.05) by Duncan’s multiple range test.
이론/모형
Louis, MO, USA) was used to enhance the MMP expression and cells were further incubated for 24 h after PMA treatment. Total protein contents of the cells were normalized using the Bradford protein determination method. Next, cell culture medium was subjected to substrate-gel electrophoresis.
성능/효과
In conclusion, extracts from H. fusiformis were able to inhibit both MMP activity and intracellular MMP pathways, regulated through TIMP expression. The bioactive compounds behind the anti-MMP effect of H.
후속연구
fusiformis and its constituents will provide valuable insights for its utilization as a functional food and future studies on its action mechanism is urged to better understand its potential. Further examinations are required to elucidate the effective substances of H. fusiformis and evaluate their mechanisms of action in order to facilitate the utilization in the development of nutraceuticals with MMP inhibitory properties. Nevertheless, in the current state, H.
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