• Title/Summary/Keyword: matrix metalloproteases

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The Anticancer Role of Capsaicin in Experimentally-induced Lung Carcinogenesis

  • Anandakumar, Pandi;Kamaraj, Sattu;Jagan, Sundaram;Ramakrishnan, Gopalakrishnan;Asokkumar, Selvamani;Naveenkumar, Chandrashekar;Raghunandhakumar, Subramanian;Vanitha, Manickam Kalappan;Devaki, Thiruvengadam
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.19-25
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    • 2015
  • Objectives: Capsaicin (CAP) is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a) pyrene (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks to induce lung cancer at the end of $14^{th}$ week. CAP was administrated (10 mg/kg body weight dissolved in olive oil) intraperitoneally. Extracellular matrix components were assayed; Masson's trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(a)pyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline), elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(a)pyrene along with CAP supplemented animals when compared to benzo(a) pyrene alone supplemented animals. The results of Masson's trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti-cancer role working against experimentally induced lung carcinogenesis.

NMMP1, a Matrix Metalloprotease in Nicotiana benthamiana Has a Role in Protection against Bacterial Infection

  • Kang, So-Ra;Oh, Sang-Keun;Kim, Jong-Joo;Choi, Do-Il;Baek, Kwang-Hyun
    • The Plant Pathology Journal
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    • v.26 no.4
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    • pp.402-408
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    • 2010
  • Plant matrix metalloproteases (MMPs) are a family of apoplastic metalloproteases closely related to human matrilysins. Up-regulation of Nicotiana benthamiana matrix metalloprotease 1 (NMMP1) expression by treatment with pathogens, ethephon and aging indicates that the gene is related to plant defense and the aging process through ethylene signaling. NMMP1 expression was higher than in normal growth leaves following infection with an incompatible pathogen Pseudomonas syringae pv. tomato T1 or a compatible pathogen P. syringae pv. tabaci and in aged leaves. Transient overexpression of NMMP1 in N. benthamiana leaves lowered the growth of P. syringae pv. tabaci. However, NMMP1-silenced leaves showed increased growth of P. syringae pv. tabaci. These data strongly suggest that NMMP1 in N. benthamiana is a defense related gene, which is positively regulated by ethylene.

Retrovirus-mediated Gene Delivery of TIMP-2 Inhibits Invasiveness, Motility and Angiogenesis

  • Ahn, Seong-Min;Seojin Jeong;Kim, Yeon-Soo;Yeowon Sohn;Aree Moon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.143-143
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    • 2003
  • The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. An endogenous inhibitor of MMP, tissue inhibitor of metalloprotease-2 (TIMP-2), has high specificity for MMP-2. An imbalance between MMP-2 and TIMP-2 causes the degradation of the extracellular matrix associated with pathological events including invasion, metastasis and angiogenesis.(omitted)

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The Fragments of Fibronectin (Fn-fr's 70, 45 kDa) Increase MMP-1 Expression and MMP-2 Activity in Normal Human Fibroblasts (사람 피부 섬유아세포에서의 파이브로넥틴 조각(70, 45 kDa)에 의한 MMP-1 발현 증가와 MMP-2 활성 증가 연구)

  • Hwang, Jae-Sung;Kim, Hyae-Kyoung;Son, Eui-Dong;Lee, Jin-Young;Kang, Hak-Hee;Chang, Ih-Seop
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.4
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    • pp.245-249
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    • 2007
  • The alternation of extracellular matrix (ECM) protein in aging process is associated with symptoms such as wrinkling and loss of elasticity in skin. Now, the major target proteins for anti-aging have been metalloproteases and the structural proteins such as collagen and elastin. Recently, the interaction of cell and ECM proteins (collagen, fibrillin, and fibronectin) is reported to have an important role in survival, proliferation and tissue reconstruction. Fibronectin is a matrix adhesion protein which binds to collagen and integrin and degraded by serine proteases. It has been reported that fragments of fibronectin (Fn-fr's) were involved in matrix metalloproteases (MMPs) expression in osteoblast. But, the role of Fn-fr's in human skin and in skin cells has not been reported yet. Therefore, we investigated the differences of fibronectin fragmentation pattern between young and aged human skin, and demonstrated that the fragmentation of fibronectins is significantly increased in aged human skin. Also, treatment of Fn-fr's (70, 45 kDa) increased MMP-1 expression and MMP-2 activity in human dermal fibroblasts. Our results suggest that Fn-fr's as a potential new factor to accelerate skin aging.

Inhibitory effect of 2-amino-3-ethoxycarbonyl-1-methyl pyrolo (3,2-b) naphtho-4,9-dione on tumor cell invasion in human fibrosarcoma cells by downregulating matrix metalloproteinase-2 and 9

  • Park, Hyen-Joo;Hwang, Hye-Jin;Lee, Hyun-Jung;Suh, Myung-Eun;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.243.1-243.1
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    • 2002
  • Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis by matrix degradation. To analyze the effect of 2-amino-3-ethoxycarbonyl-1-methyl pyrolo (3,2-b) naphtho-4,9-dione (compound 1) on the invasion or metastasis of cancer cells the expression of matrix metalloproteases (MMPs) was investigated in human fibrosarcoma HT 1080 cells by AT -PCR or gelatin zymographic methods. (omitted)

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Inhibitory effect of DA-125 on cancer metastasis by downregulating MMPs and CAMs

  • Park, Hyen-Joo;Hwang, Hye-Jin;Kim, Won-Bae;Kim, Soon-Hoe;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.68.3-69
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    • 2003
  • Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis by extracellular matrix degradation. To analyze the effect of DA-125, a anthracyclin derivative, on the invasion or metastasis of cancer cells the expression of matrix metalloproteases (MMPs) was investigated in human fibrosarcoma HTl080 cells by RT-PCR or gelatin zymographic methods. As result, DA-125 suppressed the expression of MMP-2 and 9 as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) TIMP-2 and MT1-MMP with a time- and dose-dependent manner. Inaddition, DA-125 inhibited cancer cell migration and colony formation, and also exhibited the inhibitory activities of invasion and motility with a matrigel and type I collagen assay. (omitted)

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RETROVIRUS-MEDIATED DELIVERY OF TIMP-2 SUPPRESSES MMP-2 SECRETION AND INVASION: A GENE THERAPY APPROACH

  • Ahn, Seong-Min;Yeowon Sohn;Kim, Yun-Soo;Aree Moon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.200-200
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    • 2001
  • The matrix metalloproteases (MMPs) play important roles in metastasis and invasion in various cell types. An endogenous inhibitor of MMP, tissue inhibitor of metalloprotease-2 (TIMP-2), has high specificity for MMP-2. An imbalance between MMP-2 and TIMP-2 causes the degradation of the extracellular matrix associated with pathological events including invasion and metastasis. Since TIMPs are secreted molecules, they have the potential to be used for gene therapy of certain tumors. (omitted)

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Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells

  • Kim, Jin-Joo;Ha, Hwa-Ae;Kim, Hee-Sun;Kim, Woo-Kyoung
    • Nutrition Research and Practice
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    • v.5 no.5
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    • pp.375-380
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    • 2011
  • This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol$/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 ${\mu}mol$/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P<0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P<0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P<0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.

TIMP-2 Overexpression by Retrovirus Effectively Inhibits Invasive Phenotype - A Gene Therapy Approach

  • Ahn, Seong-Min;Yeowon Sohn;Kim, Yun-Soo;Aree Moon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.106-106
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    • 2001
  • Matrix metalloproteases (MMPs) 는 다양한 세포에서 전이와 침윤성에 중요한 역할을 한다. MMP의 내인성 저해제인 tissue inhibitor of motalloprotease-2 (TIMP-2) 는 MMP-2에 높은 특이성을 지닌다. MMP-2와 TIMP-2사이의 불균형은 침윤성과 전이와 같은 병리학적 과정과 관계되는 extracellular matrix (ECM)의 퇴화를 일으킨다. TIMPs는 분비되는 분자이기 때문에 특정한 암의 유전자 치료에 사용될 가능성을 지닌다. 본 연구에서는 MMP-2가 H-ras에 의해 유도된 침윤성에 책임지는 것으로 보여지는 H-ras MCF10A 세포에 TIMP-2 유전자를 함유하는 retrovirus를 이용하여 연구하였다. TIMP-2 유전자를 함유하는 재조합 retrovirus는 PG13 세포를 infection 시키는데 사용되었다. H-ras MCF10A 세포는 PGl3 세포의 conditioned media로 처리되었을 때, gelatin zymography에서 MMP-2의 분비가 농도의존적으로 저해되었다. 또한 retrovirus에 의한 TIMP-2의 과잉 발현은 농도의존적으로 H-ras MCF10A 세포의 침윤성과 이동성을 상당히 감소시킨다. 이와 같은 실험 결과는 TIMP-2가 H-ras MCF10A 세포에서 MMP-2 분비와 세포의 침윤성, 이동성을 감소시키는 역할을 지닌다는 것과 TIMP-2 유전자를 함유하는 retrovirus가 효과적으로 MMP-2 분비, 세포 침윤성, 세포 이동성을 감소시켰다는 것을 보여 준다. 이는 암의 예방과 치료를 위한 유전자 치료법의 적용에 상당한 가능성을 제시한다.

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Retroviral Delivery of TIMP-2 Inhibits H-ras-induced Migration and Invasion in MCF10A Human Breast Epithelial Cells

  • Ahn, Seong-Min;Jeong, Seo-Jin;Kim, Yeon-Soon;Sohn, Yeo-Won;Moon, Aree
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.168.3-169
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    • 2003
  • The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenopus inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsible for the H-ras-induced invasive and migrative phenotypes in MCF10A human breast epithelial cells. Here, we investigated the effect of TlMP-2 overexpression on invasion and migration in H-ras MCF10A cells. (omitted)

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