• Preventive Nutrition and Food Science
• /
• 제22권3호
• /
• pp.184-190
• /
• 2017

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.

• Biomolecules & Therapeutics
• /
• 제17권4호
• /
• pp.422-429
• /
• 2009

Invasion and metastasis is the main cause of cancer mortality. Angiogenesis is a prerequisite for the tumor growth and metastasis. Matrix metalloproteinases (MMPs) are the key enzymes playing in the invasive growth and metastasis of cancer as well as angiogenesis. Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L), has been reported to suppress cancer invasion and angiogenesis. In the present study, we investigated the antiinvasive effects of xanthohumol (1) and its synthetic derivatives, 4'-O-methylxanthohumol SEM ether (2), xanthohumol C (3), and xanthohumol C MOM ether (4) in relation to MMP expression in HT-1080 human fibrosarcoma cells. The compound 1 and its derivative, 3 and 4, significantly inhibited serum-induced HT-1080 cell invasion, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced activity and expression level of MMP-2 and MMP-9 in a concentration-dependant manner. In addition, they inhibited TPA-enhanced expression of MT1-MMP with relatively weak inhibition in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 level. The compound 1 significantly decreased the cell viability, whereas the derivatives, 2 and 3 showed no cytotoxicity, and compound 4 showed slight cytotoxicity in the cells. Furthermore, in a chick chorioallantoic membrane (CAM) assay, the derivatives 3 and 4 dose-dependently suppressed vascular endothelial growth factor (VEGF)-induced angiogenesis, which is similar to that of compound 1. Taken together, the results indicate that compounds 3 and 4 may be valuable anti-angiogenic agents in the treatment of chronic diseases such as cancer and inflammation working through suppression of MMP-2 and MMP-9.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 춘계학술대회 논문집
• /
• pp.41-42
• /
• 2003

Matrix metalloproteinases (MMPs) inhibitors were screened from Metasequoia glyptostroboides and one potent inhibitor, dihydrohinokiflavone (DHHF), a biflavonoid, was selected. DHHF inhibited proliferation of HT1080, human fibrosarcoma cells in a dose-dependent manner. Noncytotoxic levels of DHHF dramatically decreased MMP-9 and MMP-2 production in unistimulated cells, but did not change the level of tissue inhibited of metalloproteinase (TIMP)-1, an inhibitor of MMP-9.(omitted)

• 한국식품영양과학회지
• /
• 제38권7호
• /
• pp.832-838
• /
• 2009

저온 진공 공정으로 건조된 비트를 유기용매로 추출하여 이들 비트 추출물 및 분획물들에 의한 인체 결장암 및 위암세포에 대한 증식 및 세포 내 활성산소종 억제 효과에 대해 검토하였다. 인체 결장암세포(HT-29)의 경우, A+M 추출물은 0.5 mg/mL 첨가농도에서 65%의 암세포 증식 억제효과를 나타내었고(p<0.05), MeOH 추출물은 A+M 추출물과 비교하였을 때 전반적으로 낮은 활성을 나타내었음을 관찰하였다. 건조 비트 추출물을 hexane, 85% aq. MeOH, BuOH, water로 다시 추출하여 얻어진 각각의 분획물들을 농도별로 처리하였을 때 특히 hexane 및 85% aq. MeOH 분획물은 낮은 농도에서부터 활성을 나타내어 0.5 mg/mL 농도에서 76% 이상의 높은 암세포 증식 억제효과(p<0.05)를 나타내었다. 인체 위암세포(AGS)에 대한 결과에서 A+M 추출물은 인체 결장암세포(HT-29)의 결과와 비교했을 때 암세포증식 억제효과가 높았고, MeOH 추출물은 A+M 추출물에 비해 낮은 활성을 나타내었으나 앞서 인체 결장암세포(HT-29)에 비해 다소 높은 암세포 성장 억제효과를 보였다. 건조 비트 추출물의 분획물들을 농도별로 인체 위암세포(AGS)에 처리했을 때 hexane과 85% aq. MeOH 분획물은 앞서의 인체 결장암세포(HT-29)의 결과와 유사하게 낮은 농도에서부터 활성이 나타나 0.25 mg/mL 이상의 농도에서 77% 이상의 억제효과가 나타났다. 인체 섬유육종세포(HT1080) 내 활성산소종 억제 실험에서 건조 비트 A+M 및 MeOH 추출물은 농도 의존적으로 측정시간 120분 동안 $500{\mu}M$ $H_2O_2$만을 처리한 control군에 비해 세포 내 활성산소종을 크게 억제시켰다. 건조 비트 분획물들을 인체 섬유육종세포(HT1080)에 처리했을 때 첨가농도 0.1 mg/mL로 처리하였을 때 BuOH 분획물을 제외한 기타 분획물들의 경우 control군보다는 낮은 수치를 나타내어 우수한 항산화 활성을 보였다. 첨가농도 0.25 mg/mL에서 85% aq. MeOH 분획물은 세포 내 활성산소종을 감소시키는데 우수한 능력을 나타내었고 hexane과 BuOH 분획물은 $500{\mu}M$ $H_2O_2$만을 처리한 control군에 비해서는 활성산소종을 감소시켰으나 blank 군보다는 높았다. 따라서 세포 내 활성산소종 감소에 의한 항산화 활성은 85% aq. MeOH 분획물에서 높았고 water 분획물의 효과가 가장 낮았음을 살펴 볼 수가 있었다.

• 한국식품영양과학회지
• /
• 제27권1호
• /
• pp.157-162
• /
• 1998

The antimutagenic activity of three kinds of extract such as fresh juice, ethanol extract and water extract of Artemisia iwayomogi against 3 - amino - 1, 4 - dimethyl - 5H - pyrido [4,3-b] indol (Trp-P-1) and N - methyl - N' - nitro - N -nitrosoguanidine(MNNG) was demonstrated with the Salmonella typhimurium assay. The number of revertants per plate decreased significantly when these extracts(0.5ug/plate) added to the assay system system using S. typhimurium TA 100. These extracts also showed prominant cytotoxic activity against four different kinds of human cancer cell as human lung cancer cell (A549), breast cancer cell(MCF7), fibrosacoma cell(HT1080) and gastric cancer cell(KATOIII), respectively.

• 생약학회지
• /
• 제32권3호통권126호
• /
• pp.189-192
• /
• 2001

Scillascilloside E-3 (1) and E-1 (2) were isolated from the bulbs of Scilla scilloides. The cytotoxic activities of these compounds were tested against murine (B16/F-10, 3LL) and human cancer cell lines (MCF7, PC-3, HT29, LOX-IMVI, A549 and HT1080). These compounds exhibited a significant cytotoxic activities against all tested cancer cells. Futhermore, the contents of 1 and 2 in S. scilloides are 43.2 and 27.9 mg/kg, respectively.

• Archives of Pharmacal Research
• /
• 제28권3호
• /
• pp.290-293
• /
• 2005

A known monoalkyl glycerol ether, ($\pm$)-1-nonadecyloxy-2,3-propanediol (1) was isolated from the ethyl acetate extract of a soft coral Dendronephthya gigantea as a weakly cytotoxic constituent against four human cancer cell lines, A549, HT-29, HT-1080, and SNU-638. In addition, a known ceramide, (28,3R,4E,8E)-N-hexadecanoyl-2-amino-4,8-octadecadiene-1 ,3-diol (2), was also isolated as an inactive constituent. This is the first report on the isolation of the compounds 1 and 2 from the octocoral, Dendronephthya species.

• 대한암한의학회지
• /
• 제15권1호
• /
• pp.47-61
• /
• 2010

Objective : The aim of this present study is to evaluate the inhibitory effect of allergen removed Rhus verniciflua (ARV) on Matrix Metalloproteinase-9 (MMP-9), Matrix Metalloproteinase-2 (MMP-2) which is considered to have a clinically important role in tumor metastasis. Methods : The inhibitory effects of standardized extract of ARV on the MMP-2, MMP-9 were investigated by spectrofluorometer while the inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 were investigated by zymography. Antimetastatic effect of standardized extract of ARV was investigated in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel. Results : The standardized extract of ARV showed inhibitory effects on the active MMP-2 (IC50, $1.01{\mu}g$/ml), active MMP-9 (IC50, $2.5{\mu}g$/ml) depending on concentrations which was determined by spectrofluorometer. The standardized extract of ARV showed inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 depending on concentrations which was determined by zymography. However its inhibitory effect on pro MMP-9 was relatively weaker rather than active MMP-2, pro MMP-2. The standardized extract of ARV showed inhibitory effects in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel according to concentration. Conclusions : These results indicate that standardized extract of ARV has antimetastatic effect through inhibit again MMP-2, MMP-9. Also its inhibitory effect is more powerful on active MMP-2, pro MMP-2 than on active MMP-9, pro MMP-9. It is necessary to conduct further studies on other MMP families, TIMP, and each component of standardized extract of ARV.

• 대한한방종양학회지
• /
• 제5권1호
• /
• pp.61-75
• /
• 1999

To examine the effect of Xuefuzhuyutang on the metastasis of cancer, the following experiments were carried out. Before the main experiments, the cytotoxicity was measured by putting Xuefuzhuyutant sample in HT1080. Then zymography was made to examine the change of gelatinolytic activity. Western blotting was carried out to examine the changes of Fos, Jun, Ets, Erk, md JNK. In vitro invasion assay with transwells coated by collagen and matrigel was carried out. From the above results the following conclusions were obtained. 1. The experimental result about cytotoxicity of Xuefuzhuyutang agaitst HT1080 was a below. The stained cell count after being treated by by Xuefuzhuyutang sample $400{\mu}g/ml$ for 24 hours was 0.9% of total cells, and the stained cell count by Xuefuzhuyutang sample $100{\mu}g/ml$ was 1.5% of total cells. Both were near the level of control group which showed 0.6% stained. 2. The result of collagenase assay was as below. In Xuefuzhuyutang sample $400{\mu}g/ml$, MMP2 was reduced as compared with TPA control group, and the band of MMP-9 induced by TPA disapappeared. In Xuefuzhuyutang samle $800{\mu}g/ml$ both bands of MMP-2 and MMP-9 disapeared. 3. The results of western blots for Jun, Fos, Ets, Erk, JNK were a below. In Xuefuzhuyutang sample $200{\mu}g/ml$, Ets was reduced, and Jun, Fos were increased. 4 The result of invasion assay was as below. The number of cells which migrated across transwell membrane in Xuefuzhuyutang-treated group was less than that of control(+TPA) group. From the above results, it was concluded that Xuefuzhuyutang might inhibit the activity of collagenase not by the MMP-2, MMP-9 promoter but by the other way.

• 고려인삼학회:학술대회논문집
• /
• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
• /
• pp.224-230
• /
• 1998

This study showed the anti-invasive activity of ginseng components, panaxadiol (PD) and panamatrlol (PT) on the highly metastatic HT1080 human flbrosarcoma cell line. PD and PT reduced tumor cell invasion through a reconstitute basement membrane in the transwell chamber. A significant down regulation of MMP-9 by PD and PT was detected by northern blot analysis. However, MMP-2 was constantly expressed. Quantitative gelatin based zymography confirmed a marked reduced expression of MMP-9 but not MMP-2 in the treatment of PD and PT. Since the chemical structures of PD and PT are very similar to that of dexamethasone, a synthetic glucocorticoid, it was investigated whether PD and PT act through GR. Western blot analysis and immunocytochemistry showed that PD and PT increased the GR fraction in the nucleus. These results suggest that ursolic acid may induce repression of MMP-9 by stimulating the nuclear translocation of GR and hence inhibiting the activity of AP-1 to TPA-responsible element of MMP-9 promoter region. In conclusion, we suggest that CR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT 1080 cells.