• KSBB Journal
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• 제23권2호
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• pp.142-146
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• 2008

본 연구에서는 U-373-MG 세포를 이용하여 오디 추출물과 VEGF에 의한 MMPs 및 플라스민의 분비에 미치는 영향을 확인하고자 하였다. U-373-MG 세포에 오디 추출물을 $100{\sim}600\;{\mu}g/mL$의 농도로 처리한 결과, MMP-2의 분비는 거의 완벽하게 억제되었고 MMP-9의 분비는 약 $1.6{\sim}5.9$배 증가하였다. 이에 비해 플라스민의 분비는 오디 추출물 농도 $500{\sim}600\;{\mu}g/mL$에서 $36%{\sim}58%$ 감소하였다. 오디 추출물과 VEGF를 병용처리한 경우, MMP-2의 분비는 VEGF만을 처리한 것과 비교하여 약 85.5% 감소하였고, MMP-9의 분비는 약 89.8% 감소하였다. 또한, U-373-MG 세포에서 오디 추출물($100\;{\mu}g/mL$)에 의한 MMP-2와 MMP-9의 분비 증가와 플라스민 분비증가는 PI 3'-kinase 경로에 의존적이었다. 본 연구 결과를 통해 오디 추출물이 VEGF의 과발현에 따른 암의 성장을 억제 조절하는데 이용될 수 있는 가능성을 확인하였다.

• Preventive Nutrition and Food Science
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• 제20권3호
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• pp.153-161
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• 2015

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.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.199-204
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• 2010

The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.

• Tuberculosis and Respiratory Diseases
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• 제52권2호
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• pp.107-116
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• 2002

연구배경 : Matrix metalloproteinase(MMP)는 세포외 기질중 기저막의 용해 및 혈관 생성에 관여하여 전이를 일으키며, 이중 MMP-9 과 STR-3 가 폐암에서 발현된 경우 예후가 나쁘며 림프절 전이와 연관이 있다는 보고가 있다. 말초혈액에서 MMP-9와 STR-3의 발현이 폐암의 진단 표지자로 사용될 수 있는 지를 평가하고 자하였다. 방 법 : 44명의 폐암 환자, 19명의 감염성 폐질환 환자, 33명의 정상인의 혈액을 채취하여 단핵구를 분리하여 MMP-9과 STR-3의 RT-PCR을 시행하였고, 혈청내 MMP-9 단백질을 ELISA로 측정하여 비교 분석하였다. 결 과 : MMP-9은 폐암환자 (26/44, 59.1%)와 정상 대조군(23/33, 69.7%)에 비해 폐감염환자 (18/19, 94.7%)에서 유의하게 높게 발현되며(p=0.018), STR-3은 폐감염환자(8/19, 42.1%)와 정상 대조군 (20/33, 60.6%)에 비해 폐암환자(37/44, 84.1%)에서 유의하게 높게 발현되었다(p=0.003). MMP-9는 폐암 환자들 사이에서 림프절 전이가 있는 군(17/24, 70.8%)에서 없는 군 (3/13, 23.1%)보다 유의하게 높게 발현되었으며(p=0.005), 그 이외에 T 병기, 원격전이 유무, 종양의 병리소견, 연령, 성별에 따른 MMP-9과 STR-3 mRNA의 발현차이는 관찰되지 않았다. 세 군간 혈청내 MMP-9 농도의 차이는 관찰되지 않았다. 결 론 : RT-PCR을 이용한 말초혈액 단핵세포에서의 STR-3 mRNA 발현 측정은 폐암의 진단 표지자로 사용될 가능성이 있을 것으로 사료된다.

• Toxicological Research
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• 제26권1호
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• pp.61-66
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• 2010

Retinoids have many beneficial effects on dermatological applications. But, retinoids cause skin irritation. In this study, the safety of retinoids was clarified via both primary skin irritation test in rabbits and sensitization study using an integrated model for the differentiation of chemical-induced allergic and irritant skin reaction (IMDS), an alternative method to sensitization test. The effects of retinoids on the change of ultraviolet A (UVA)-induced matrix metalloproteinase-1 (MMP-1) in human skin fibroblasts and the modulation of type-1 pN collagen synthesis in hairless mice were examined to clarify the anti-wrinkle effects. Alltrans retinol (t-ROL) and its derivative, all-trans retinoic acid (t-RA), showed mild skin irritation but did not induce the sensitization. t-ROL and t-RA exerted anti-wrinkle effects by inhibiting the UVA-induced MMP-1 in human skin fibroblasts and increasing the type-1 pN collagen synthesis in hairless mice. These findings suggest that retinoids do not induce the allergy, and show anti-wrinkle effects by decreasing MMP-1 activation and increasing collagen synthesis.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.730-733
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• 2004

Bioassay-guided fractionation has led to the isolation of triterpenoid saponins such as Acutoside A (3-O-[O-${\beta}$-D-glucopyrano$yl-(1${\to}$2)-O-${\beta}$-D-glucopyranosyl] oleanolic acid) from the whole plants of Viola hondoensis. Among them, Saponin 1 exhibited potent inhibitory activity against matrix metalloproteinase (MMP)-1, and prevented the UV-induced changes in the MMP-1 expression. In addition, compound was isolated from this plant for the first time.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3681-3684
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• 2013

Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 in human osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then the precise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expression vector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantly suppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwells were dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasion and metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This was confirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9 protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomas by down-regulating TIAM1, MMP2 and MMP9 expression.

• 대한약침학회지
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• 제21권3호
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• pp.177-184
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• 2018

Objectives: Auraptene, a natural citrus coumarin, found in plants of Rutaceae and Apiaceae families. In this study, we investigated the effects of auraptene on tumor migration, invasion and matrix metalloproteinase (MMP)-2 and -9 enzymes activity. Methods: The effects of auraptene on the viability of A2780 and Hela cell lines was evaluated by MTT assay. Wound healing migration assay and Boyden chamber assay were determined the effect of auraptene on migration and cell invasion, respectively. MMP-2 and MMP-9 activities were analyzed by gelatin zymography assay. Results: Auraptene reduced A2780 cell viability. The results showed that auraptene inhibited in vitro migration and invasion of both cells. Furthermore, cell invasion ability suppressed at $100{\mu}M$ auraptene in Hela cells and at 25, $50{\mu}M$ in A2780 cell line. Gelatin zymography showed that for Hela cell line, auraptene suppressed MMP-2 enzymatic activity in all concentrations and for MMP-9 at a concentration between 12.5 to $100{\mu}M$ in A2780 cell line. Conclusion: Auraptene inhibited migration and invasion of human cervical and ovarian cancer cells in vitro by possibly inhibitory effects on MMP-2 and MMP-9 activity.

• 한국발생생물학회지:발생과생식
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• 제3권1호
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• pp.29-38
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• 1999

자궁내막증은 흔한 부인과적 질병이며 여성 불임의 한 원인이 되나 그 발생 원인에 대하여서는 아직 논란의 여지가 많다. 최근 월경혈의 역류가 한 원인이며 자궁내막증 환자가 정상여성에서 보다 역류되는 월경혈의 양이 많거나 침습성이 강한 것이 자궁내막증의 발생 원인이 될 수 있다는 이론들이 소개되었다. 종양이나 자궁내막 조직의 침습이나 전이에는 세포막외 기질 및 기저막의 파괴가 일어나야 하는데 이 과정에 plasminogen activators (PAs)나 matrix metalloproteinase (MMPs)같은 proteolytic enzyme이 관여한다. 이에 자궁 내막증환자와 대조군의 자궁내막에서 PA나 MMP를 억제하는 plasminogen activator inhibitor-1 (PAI-1)나 tissue inhibitor of metalloproteinase (TIMP-3)의 mRNA 발현의 차이를 quantitative competitive RT PCR로 연구하였으며, 그 결과 자궁내막증 환자의 황체기 자궁내막에서는 정상 대조군 환자에서 보다 PAI-1과 TIMP-3 mRNA발현이 낮음을 알 수 있었다. 따라서 자궁내막증 환자의 자궁내막에서는 PA와 MMP의 활성도가 증가할 수 있으며 이 증가된 proteolytic activity로 인하여 역류된 자궁내 막 조직의 복강내 침습이 보다 쉽게 일어날 가능성이 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5747-5751
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• 2014

Background: Coptisine, an isoquinoline alkaloid extracted from Coptidis rhizoma, has many biological activities such as antidiabetic, antimicrobial and antiviral actions. However, whether coptisine exerts anti-cancer metastasis effects remains unknown. Materials and Methods: Effects of coptisine on highly metastatic human breast cancer cell MDA-MB-231 proliferation were evaluated by trypan blue assay and on cell adhesion, migration and invasion by gelatin adhesion, wound-healing and matrigel invasion chamber assays, respectively. Expression of two matrix metalloproteinases (MMPs), MMP-9, MMP-2 and their specific inhibitors tissue inhibitor of metalloproteinase 1 (TIMP-1) and tissue inhibitor of metalloproteinase 2 (TIMP-2) were analyzed by RT-PCR. Results: Coptisine obviously inhibited adhesion to an ECM-coated substrate, wound healing migration, and invasion through the matrigel in MDA-MB-231 breast cancer cells. RT-PCR revealed that coptisine reduced the expression of the ECM degradation-associated gene MMP-9 at the mRNA level, and the expression of TIMP-1 was upregulated in MDA-MB-231 cells, while the expression of MMP-2 and its specific inhibitor TIMP-2 was not affected. Conclusions: Taken together, our data showed that coptisine suppressed adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function. Coptisine might be a potential drug candidate for breast cancer therapy.