• Biomolecules & Therapeutics
• /
• 제29권1호
• /
• pp.64-72
• /
• 2021

Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of Nigella sativa, has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E2 (PGE2) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE2 agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprost-induced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE2-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.

• 한방안이비인후피부과학회지
• /
• 제36권1호
• /
• pp.40-49
• /
• 2023

Objectives : This study was conducted to confirm the skin anti-aging effect of Chungpyesagan-tang(CPSGT) extract. Methods : We performed MMT assay to confirm the cytotoxicity of CPSGT. After inducing matrix metalloproteinase-1(MMP-1) with tumor necrosis factor-α(TNF-α), we investigated mRNA expression and protein secretion of MMP-1 by real-time RT-PCR and ELISA. In addition, we measured the protein expression of mitogen-activated protein kinases(MAPKs) and transcription factors by western blot. Results : CPSGT was not cytotoxic at 25-800㎍/㎖. The mRNA expression and protein secretion of MMP-1 decreased when treated with CPSGT. The protein expression of p-ERK, p-JNK, p-p38 was decreased by CPSGT. In addition, the protein expression of p-c-jun and p-NF-κB, which are transcription factors, were also decreased. Conclusion : This suggests that CPSGT can inhibit MMP-1 and thus be a potential anti-aging substance.

• BMB Reports
• /
• 제46권11호
• /
• pp.533-538
• /
• 2013

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• KSBB Journal
• /
• 제25권3호
• /
• pp.265-270
• /
• 2010

본 연구에서는 simvastatin에 의한 U-373-MG 세포의 이동 및 침윤에 미치는 효과와 그 가능한 기작에 대해 조사하였다. U-373-MG 세포의 이동에 미치는 simvastatin의 효과를 확인한 결과, $0.01\;{\mu}M$의 simvastatin에서는 U-373-MG 세포의 이동이 약 43% 증가되었으나 $1\;{\mu}M$과 $20\;{\mu}M$에서는 세포의 이동이 각각 28%와 35% 억제되었다. 세포의 침윤 역시 $0.001\;{\mu}M$의 simvastatin에서는 23%, $0.01\;{\mu}M$에서는 26%의 침윤 증가가 관찰되었으나, $1\;{\mu}M$과 $10\;{\mu}M$에서는 세포의 침윤이 각각 45%와 54%가 억제되었다. $0.001\;{\mu}M$ 과 $0.01\;{\mu}M$의 simvastatin 처리에 의해 MMP-2의 분비량이 각각 30%와 59% 증가되었으나, $10\;{\mu}M$과 $20\;{\mu}M$의 simvastatin 처리에 의해 MMP-2의 분비량은 각각 31%와 60% 감소되었다. MMP-9 및 플라스민의 분비에 미치는 simvastatin의 효과도 MMP-2에 미치는 효과와 유사하였다. Simvastatin이 MMP-2와 MMP-9 단백질의 생성에 미치는 효과를 조사한 결과, $0.001{\sim}1\;{\mu}M$의 simvastatin에서는 MMP-2와 MMP-9 생성이 증가되었으나 $10{\sim}20\;{\mu}M$에서는 MMP-2와 MMP-9의 생성이 감소되었다. 이러한 결과는 낮은 농도의 simvastatin은 혈관신생을 유도하고 높은 농도의 simvastatin은 혈관신생을 억제한다는 것을 보여주는 것이다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권16호
• /
• pp.6829-6835
• /
• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권12호
• /
• pp.4823-4827
• /
• 2014

Background: Since inconsistent results have been reported regarding the relation between the matrix metalloproteinase-2 (MMP-2) -1306C>T polymorphism and susceptibility for breast cancer, we performed a meta-analysis to investigate the issue. Materials and Methods: An internet search of PubMed and EMBASE was performed to identify eligible studies. Pooled odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated to evaluate any association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility. Results: Nine case-control studies were included in the meta-analysis, involving 9,858 cases and 10,871 controls. Overall, there was no evidence of any association between the MMP-2 -1306C>T polymorphism and breast cancer susceptibility in different genetic models (T-allele vs C-allele: OR=0.95, 95%CI, 0.82-1.10, p=0.49; TT vs CC: OR=1.03, 95%CI, 0.90-1.19, p=0.66; TT+TC vs CC: OR=0.93, 95%CI, 0.78-1.10, p=0.38; TT vs TC+CC: OR=1.02, 95%CI, 0.89-1.17, p=0.77). In the subgroup analysis by ethnicity, CC was associated with a significant increase in breast susceptibility among Latin-Americans in the dominant model (OR=0.61, 95%CI, 0.40-0.93, p=0.02), but the association disappeared in other models. No significant association was observed among Europeans, East Asians and others in different genetic models. In the subgroup analysis by their source of controls, no significant association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility was noted among population-based studies and hospital-based studies in different genetic models. Conclusions: The results of this meta-analysis suggest that MMP-2 -1306C>T polymorphism is not associated with breast cancer susceptibility, although the association among Latin-Americans in the dominant model was significant.

• 생명과학회지
• /
• 제32권12호
• /
• pp.938-946
• /
• 2022

본 연구는 대풍자 에탄올 추출물에 대한 항산화 활성 및 주름생성 억제 활성을 확인하고자 하였다. 대풍자 에탄올 추출물의 항산화 활성을 확인하기 위하여 DPPH와 ABTS⁺ radical 소거능을 측정하였고 그 결과 추출물 1,000 ㎍/ml 농도에서 각각 73.5%와 74.4%의 높은 소거능을 나타냈다. 주름생성 억제 활성을 확인하기 위하여 collagenase 저해 활성을 실험하였으며, 그 결과 추출물 1,000 ㎍/ml 농도에서 78.8%의 유의할만한 우수한 결과를 보였다. 또한 추출물에 대한 세포의 독성을 확인하기 위해 MTT assay를 수행하였으며, 50 ㎍/ml 이하의 농도에서 약 91.7%의 생존율을 보여, 이후의 세포 실험은 50 ㎍/ml 이하의 농도에서 진행하였다. 섬유아세포인 CCD-986sk에 UVB (20 mJ/cm²)의 자극을 주고 대풍자 에탄올 추출물을 농도별로 처치한 후 procollagen type I과 MMP-1의 발현에 대한 영향을 확인하고자 ELISA 및 RT-PCR 분석을 하였다. 그 결과 대풍자 에탄올 추출물은 PIP의 생합성과 mRNA 발현은 농도의존적으로 증가하였으며, 특히 UVB만 자극한 Cont (각각의 생합성율은 50.3%와 45.8%)과 비교하였을 때 50 ㎍/ml의 농도에서 각각 약 64.2%와 83.4%의 생합성을 보였다. MMP-1의 protein과 mRNA 발현에 대한 결과는 농도의존적으로 감소했음을 확인하였으며, 50 ㎍/ml의 농도에서 각각 약 48.7%와 35.9%의 낮은 발현율을 보였다. 이와 같은 결과를 바탕으로 본 연구는 대풍자 에탄올 추출물이 주름억제 기능성 소재로써의 활용 가능성을 제시해 줄 것으로 사료된다.

• 농업생명과학연구
• /
• 제50권2호
• /
• pp.151-160
• /
• 2016

염증성 사이토카인은 파골세포형성과정에서 중요한 요인이며, 뼈의 흡수는 자주 골다공증과 연결된다. 설포라판은 보로콜리의 화뢰로 부터 분리된 물질로 염증성 사이토카인을 억제한다고 알려져 있다. 본 실험에서는 Receptor activator of nuclear factor kappaB ligand(RANKL)로 자극된 세포에서 설포라판이 파골세포 형성 억제에 대한 효과를 측정하였다. 설포라판은 대식세포인 RAW 264.7 세포에서 파골세포 특이 마커 유전자인 tartrate-resistant acid phosphatase(TRAP), Cathepsin K, matrix metalloproteinase 9(MMP-9), calcitonin receptor을 저해하였으며, TRAP, MMP-9, tumor necrosis factor receptor-associated factor 6(TRAF6)와 전사인자인 nuclease factor of activated T cells(NFATc1)의 단백질 발현과 RANKL로 자극하였을 때 전자인사인 nuclear factor kappaB(NF-kappaB)의 전사활성도 억제 하였다. 이와 같은 결과로 설포라판이 NF-kappaB의 전사활성 억제뿐만 아니라, 파골세포형성인자(TRAP, cathepsin K, MMP-9, calcitonin, NFATc1)와 NFATc1의 발현을 억제시키는 효과가 있음을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권11호
• /
• pp.4751-4758
• /
• 2015

Echinodermata use saponins in chemical defense against pathogens and predators. The molecular mechanisms of antimetastatic effects of brittle star saponins are still unknown. The present study examined antioxidant capacity and invasive ability in HeLa carcinoma cells exposed to brittle star crude saponins. Discolorating methods with DPPH and ABTS and expression of SOD-2 with RT-PCR were used to estimate the antioxidant activity. The anti-invasive activity of extracted saponins was examined through adhesion of HeLa cells to extracellular matrix, wound healing and evaluation of the mRNA levels of MMP-2 and MMP-9 by real time-PCR. The results showed that extracted saponins had cytotoxicity against cervical cancer cells and ABTS and DPPH scavenging properties with $IC_{50}$ values of 604.5, $1012{\mu}g/ml$, respectively. Further, we found that, in wound healing assay, brittle star saponins could prevent invasion of HeLa cells in a concentration dependent manner. Furthermore, cell adhesion assay demonstrated blockage of cell attachment to extracellular matrix with an $IC_{50}$ concentration of $16.1{\mu}g/ml$. The significant dose dependent down regulation of MMP-2 and MMP-9 in treated cells demonstrated that isolated saponins can decline tumor metastasis in vitro. The brittle star saponins remarkably prevented cervical cancer invasion and migration associated with down regulation of matrix metalloproteinase expression. Therefore, saponins could be suggested as an anti-invasive candidate against cervical cancer and an antioxidant as well.

• 생명과학회지
• /
• 제21권11호
• /
• pp.1501-1510
• /
• 2011

최근에 해양자원에 있는 동물, 해조류 곰팡이 세균에서 신규 잠재적인 후보약효제가 조사되어 왔다. 본 연구에서는 치료제를 탐색하기 위하여 암전이, 관절염, 만성염증 및 주름형성에 주요한 역할을 하는 기질금속단백질분해효소(s) (MMPs)를 목적효소로 이용하였다. 5종의 녹조류, 18종의 홍조류, 4종의 갈조류를 포함한 다양한 해조류가 사람피부섬유아세포 및 섬유아육종세포로부터 유래된 기질금속단백질효소에 미치는 영향을 gelatin zymography를 이용하여 조사하였다. 사람피부섬유아세포에서는 홍조류중에서 Laurencia okamurae, Polysiphonia japonica, Grateloupia lanceolate 및 Sinkoraena lancifolia에서 MMP-2 억제효과가 관찰되었다. 반면에 녹조류의 Enteromorpha compressa와 Enteromorpha linza, 갈조류의 Peltaronia bighamiae and Sargassum thunbergii에서는 MMP-2 활성화가 관찰되었다. 사람섬유아육종세포에서는 MMP-9 활성화가 갈조류인 Sargassum thunbergii, 홍조류의 Polysiphonia japonica, 녹조류의 Enteromorpha compressa와 Enteromorpha linza의 존재 하에서는 감소되었다. 본 연구에서 흥미로운 발견은 녹조류의 E. compressa와 E. linza 및 갈조류의 S. thunbergii는 정상세포에서는 MMP-2에 대하여 활성화 효과를 나타내었으나, 암세포에서는 MMP-9응 억제하는 효과를 나타낸 것이다. 이러한 결과는 녹조류의 E. compressa와 E. linza 및 갈조류의 S. thunbergii는 항암 효능을 발휘할 수 있는 성분을 함유하고 있다는 것을 암시하고 있다.