• Title, Summary, Keyword: HT1080

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Novel Suppressive Effects of Ketotifen on Migration and Invasion of MDA-MB-231 and HT-1080 Cancer Cells

  • Kim, Hyun Ji;Park, Mi Kyung;Kim, Soo Youl;Lee, Chang Hoon
    • Biomolecules & Therapeutics
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    • v.22 no.6
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    • pp.540-546
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    • 2014
  • The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

Effect of Graphene with Antioxidant Activity on Matrix Metalloproteinase in HT1080 Cells (항산화 활성을 가진 그래핀이 HT1080 세포에서 기질금속단백질분해효소에 미치는 영향)

  • Lee, Su-Gyeng;Kim, Moon-Moo;Oh, Yunghee
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1209-1215
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    • 2013
  • Graphene is an allotrope of carbon that is composed of one-atom-thick planar sheets. It is known to have a preventive effect on cancer in photothermal therapy and a protective effect in DNA oxidation. The effect of graphene on oxidative stress and matrix metalloproteinases (MMPs) was investigated in human fibrosarcoma HT1080 cells. The results showed that graphene specifically exerted an inhibitory effect on DNA oxidation, but it did not inhibit other oxidative stress. In addition, graphene decreased the expression and the activation of MMP-2 and MMP-9 stimulated by phenazine methosulfate-m, which induces the production of intracellular hydrogen peroxide. In particular, the expression of antioxidant enzymes, such as superoxide dismutase (SOD-2), was decreased in the HT1080 cells, indicating that the decrease in the expression level of SOD was due to the antioxidant effect of graphene. These results suggest that the inhibitory effect of oxidative stress in the presence of graphene could inhibit the expression of MMPs in HT1080 cells. Based on the above results, graphene may have chemoprevention properties through inhibition of MMP-2 and MMP-9 related to metastasis.

Cytotoxic Effect of Chalcone Derivatives in MCF-7 Human Breast Cancer and HT-1080 Human Fibrosarcoma Cells (Chalcone 유도체들의 사람 유방암세포주 및 사람 섬유육종 세포에 대한 세포독성효과)

  • Kang, You-Ra;Park, Min-A;Cho, Mi-Yeon;Lee, Kyung-Hee;Kim, Jung-Ae
    • YAKHAK HOEJI
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    • v.54 no.1
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    • pp.27-31
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    • 2010
  • Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L.), has been reported to suppress tumor growth. 4-hydroxychalcone and isobavachalcone are chalcone derivatives and they have similar structure with xanthohumol. In the present study, we investigated the cytotoxic activities of chalcone and its derivatives, 4-hydroxychalcone, xanthohumol, and isobavachalcone, in MCF-7 and adriamycin resistant MCF-7 (MCF-7/ADR) breast cancer cells and HT-1080 fibrosarcoma cells. In a cell viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reagent, chalcone and 4-hydroxychalcone decreased cell viability in HT-1080 cells, but not in MCF-7 and MCF-7/ADR cells. Isobavachalcone showed similar cytotoxicity in HT-1080 cells, and only limited cytotoxicity in MCF-7 and MCF-7/ADR cells at very high concentration (50 ${\mu}M$). In contrast, xanthohumol showed concentration-dependent cytotoxicity in MCF-7, MCF-7/ADR, and HT-1080 cancer cells. Taken together, the structure-activity relationship of chalcone and its derivatives indicate that chalcones may be valuable cytotoxic compounds against selective cancer types.

Inhibitory Effect of Naringenin on MMP-2, -9 Activity and Expression in HT-1080 Cells (HT1080 세포주에서 naringenin의 MMP-2, -9 효소 활성 및 발현 억제 효과)

  • Chae, Soo-Chul
    • Environmental health and toxicology
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    • v.24 no.1
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    • pp.63-70
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    • 2009
  • Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

Anti-metastatic Effect of Samguikoeui-Tang Via Inhibition of Matrix Metalloproteinases Activities (금속단백분해효소의 활성 저해를 통한 삼귀고의탕의 전이억제 효과)

  • Kim, Sung-Moo;Rhee, Yun-Hee;Lee, Joo-Ho;Kim, Sung-Hoon;Lee, Eun-Ok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1470-1474
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    • 2008
  • This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.

Roles of Matrix Metalloproteinase-2 and -9 on the H-ras-Induced Invasive Phenotype in Human Breast Epithelial Cells and Human Fibrosarcoma Cells

  • Kim, Mi-Sung;Won, Ju-Hye;Aree Moon
    • Toxicological Research
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    • v.14 no.4
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    • pp.569-575
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    • 1998
  • One of the most frequent dejects in human cancer is the uncontrolled activation of the ms-signaling pathways. Significant evidence has accumulated to directly implicate members of the matrix metalloproteinases (MMPs) in tumor invasion and metastasis formation. We have previously shown that MMP-9 expression was significantly enhanced in the ras-tranfected HT1080 human fibrosarcoma cells at the mRNA level. In the present study, we investigated the roles of MMP-2 and -9 on the H-ras-induced invasive phenotypes of MCF 10A human breast epithelial cells and HT 1080 human fibrosarcoma cells. We show that H-ras is able to induce or enhance a signaling pathway leading to the enhancement of an invasive phenotype in both MCF10A and HT1080 cells as determined by matrigel invasion assay. We then examined the effect of H-ras activation on the expression of MMP-2 and -9 by measuring enzymatic activities and mRNA levels. Our data clearly demonstrated that H-ras prominently induces expression of MMP-2 in MCF10A cells, while it efficiently up regulates MMP-9 in HT1080 cells. Taken together, these findings suggest that the correlation between ras-mediated invasiveness and enhanced expression of MMPs may be cell type-specific: MMP-9 is closely associated with the invasive phenotype induced by ras activation in fibrosarcoma cells, whereas MMP-2 is more likely associated with it in epithelial cells.

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Inhibition of the expression on MMP-2, 9 and morphological changes via human fibrosarcoma cell line by 6,6'-bieckol from marine alga Ecklonia cava

  • Zhang, Chen;Li, Yong;Shi, Xiujuan;Kim, Se-Kwon
    • BMB Reports
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    • v.43 no.1
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    • pp.62-68
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    • 2010
  • Matrix Metalloproteinases (MMPs) are a family of zinc-endopeptidases which can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. 6,6'-bieckol isolated and characterized from an edible marine brown alga Ecklonia cava (EC), according to the comprehensive spectral analysis of MS and NMR data. Here the influence of 6,6'-bieckol on expressions of MMPs was examined by zymography and western blot analysis via human fibrosarcoma cell line (HT1080). It is shown that 6,6'-bieckol significantly down regulated the expressions of MMP-2 and -9 in dose-dependent manner. The influence of 6,6'-bieckol on the cell viability and cell behavior of HT1080 cells were also investigated, our dates shown that it suppressed the migration and 3D culture in HT1080 cells. Meanwhile, we explored several signal pathways which may contribute to this process, and found the suppressing of MMPs expressions in HT1080 cells might be due to the suppression of NF-${\kappa}B$ signal pathway.

Angiogenic Inhibitory Effect of Zingiberis Rhizoma (건강의 혈관신생 억제효과에 관한 연구)

  • Nam Sang Choon;Myung Eu gene;Kang Hee;Shim Bum Sang;Kim Sung Hoon;Choi Seung Hoon;Ahn Kyoo Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1608-1612
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    • 2004
  • This study was conducted to investigate angiogenic inhibitory effect of Zingiberis Rhizoma methanol extract using ECV-304 cells and HT1080 fibrosarcoma cells. The viability of ECV-304 was 30% at 50㎍/㎖ of Zingiberis extract and that of HT1080 was 30% at 100㎍/㎖. Using the BrdU incorporation assay, Zingiberis inhibited the DNA synthesis of ECV-304 and HT1080 by 70% and 50% at 200㎍/㎖. In tube formation assay, at 10㎍/㎖ of Zingiberis, tube network began to degrade and at higher doses, it was completely destroyed. Zymography demonstrated that Zingiberis extract decreased MMP-9 at 10㎍/㎖ and higher doses remarkably inhibited the expression of MMP-9. These data indicate that Zingiberis Rhizoma has angiogenic inhibitory effects and shows the possibility of future anti-metastatic drug.

Gliotoxin from the marine fungus Aspergillus fumigatus induces apoptosis in HT1080 fibrosarcoma cells by downregulating NF-κB

  • Kim, Young-Sang;Park, Sun Joo
    • Fisheries and aquatic sciences
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    • v.19 no.9
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    • pp.35.1-35.6
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    • 2016
  • Gliotoxin has been recognized as an immunosuppressive agent for a long time. Recently, it was reported to have antitumor properties. However, the mechanisms by which it inhibits tumors remain unclear. Here, we showed that gliotoxin isolated from the marine fungus Aspergillus fumigatus inhibited proliferation and induced apoptosis in HT1080 human fibrosarcoma cells. Gliotoxin repressed phosphorylation-dependent degradation of $I{\kappa}B-{\alpha}$, an antagonist of nuclear factor kappa B ($NF-{\kappa}B$), which is a known tumor-promoting factor. This coincided with a decrease in nuclear import of $NF-{\kappa}B$, suggesting its signaling activity was impaired. Moreover, gliotoxin increased intracellular reactive oxygen species (ROS). Since ROS have been known to inhibit $NF-{\kappa}B$, this may also contribute to gliotoxin's antitumorigenic effects. These results suggest that gliotoxin suppressed the activation of $NF-{\kappa}B$ by inhibiting phosphorylation and degradation of $I{\kappa}B-{\alpha}$ and by increasing ROS, which resulted in apoptosis of HT1080 cells. Cumulatively, gliotoxin is a promising candidate antagonist of $NF-{\kappa}B$, and it should be investigated for its possible use as a selective inhibitor of human fibrosarcoma cells.

Inhibitory Effects of Carex pumila Extracts on MMP-2 and MMP-9 Activities in HT-1080 Cells (HT-1080 세포주에서 좀보리사초 추출물의 MMP-2와 MMP-9 활성 억제효과)

  • Kim, Junse;Kong, Chang-Suk;Seo, Youngwan
    • Ocean and Polar Research
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    • v.40 no.4
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    • pp.249-257
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    • 2018
  • Matrix metalloproteinases (MMPs) are associated with the invasion and metastasis of malignant tumors composed of cancer cells in an increased state of expression. This study evaluates the inhibitory effect of Carex pumila on MMP-2 and MMP-9 activity in phorbol-12-myristate-13-acetate (PMA)-stimulated HT-1080 human fibrosarcoma cells using gelatin zymography, MMPs enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. C. pumila was extracted twice with dichloromethane ($CH_2Cl_2$) and methanol (MeOH). Treatment with $CH_2Cl_2$ extract and MeOH extract in PMA-stimulated HT-1080 cells effectively reduced the production of MMP-2 and 9. Also, the combined crude extracts ($CH_2Cl_2$ and MeOH) significantly inhibited the enzymatic activities and the expression of MMP-2 and MMP-9 in mRNA and protein levels. The combined crude extracts were partitioned between $CH_2Cl_2$ and water. The organic layer was further fractionated with n-hexane, 85% aqueous methanol (85% aq.MeOH) and the aqueous layer was separated into n-butanol and water, successively. Of the fractions, 85% aq.MeOH fraction showed the highest inhibitory activity of MMP-2 and MMP-9 in gelatin zymography and MMP ELISA kit. Furthermore, 85% aq.MeOH fraction most significantly suppressed cell migration. In RT-PCR and Western blot assay, n-butanol and 85% aq.MeOH fractions exerted the greatest inhibition on mRNA and protein expression of MMP-2 and MMP-9, respectively. As a result, C. pumila can be used as a good anti-invasive agent source.