Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Suppression of Matrix Metalloproteinase-9 Expression of Flavonoids from Metasequoia glyptostroboides

낙우송(Metasequoia glyptostroboides)으로부터 분리한 flavonoid의 금속단백분해효소-9 발현 억제 활성

  • Yang Jae-Young (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee Ho-Jae (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kho Yung-Hee (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kwon Byoung-Mok (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Chun Hyo Kon (Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Published : 2005.04.01
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Abstract

Matrix metalloproteinases (MMPs) are a family of structurally and functionally related zinc-dependent enzymes responsible for proteolytic degradation of extracellular matrix components such as base membrane or interstitial stroma. MMPs play an important role in a variety of physiological and pathological tissue remodeling processes, including wound healing, embryo implantation, tumor invasion and metastasis. Since MMP-9 (gelatinase B) has unique ability to cleave type IV collagen, gene expression of MMP-9 has been focused on as a pharmacological target. Flavonoids are a class of compounds that are widely spread in plants. In the coures of screening for the suppressors of MMP-9 gene expression from natural products, Metasequoia glyptostroboides was selected. Six flavonoids, sciadopitysin, isoginkgetin, bilobetin, 2,3-dihydrohinokiflavone, luteolin and apigenin were purified as suppressors of MMP-9 gene expression from M. glyptostroboides. The suppressing activity of the isolated flavinoids on the MMP-9 gene expression was measured by gelatin zymography and Nothern blot analysis.

기질 금속단백분해효소(MMP)는 기저막이나 간질성 조직 등에 있는 세포외기질 성분을 분해하여 상처 치유, 태아의 발생, 종양세포의 침윤과 전이 등을 포함하여 조직이 재구성되는 과정에서 생리학적 및 병리학적인 과정 양쪽 모두에 매우 중요한 역할을 한다. 본 연구에서는 MMP-9 유전자의 발현을 억제하는 물질을 천연물에서 탐색하였고, 탐색된 시료 중에서 높은 역가를 가진 낙우송과의 Metasequoia glyptostroboides가 선택되었다. 여러 가지 flavonoid 성분을 가지고 있는 Metasequoia glyptostroboides를 이용하여 4개의 biflavonoid와 2개의 monoflavonoid 구조의 물질을 분리하였고, 이 flavonoid들은 sciadopitysin, isoginkgetin, bilobetin, 2, 3-dihydrohino-kiflavone, luteolin, apigenin으로 정제하여 구조를 밝히고 zymography, WST-1을 이용한 세포독성시험, northern blot 등의 실험을 통하여 각 화합물의 구조적인 특성과 함께 MMP-9 유전자 발현을 억제하는 효과가 있는 것을 확인하였다.

Keywords

References

  1. Christelle Benaud, Rober B. Dickson, Erik W. Thompson. 1998. Roles of the matrix metalloproteinases in mammary gland development and cancer. Breast Cancer Research and Treatment 50, 97-116 https://doi.org/10.1023/A:1006061115909
  2. Clare M. Dollery, Jean R. McEwan, Adriano M. Henny. 1995. Matrix Metalloproteinases and Cardiovascular Disease. Circ Res. 77
  3. Hee Kee Kim, Kun Ho Son, Hyeun Wook Chang, Sam sik Kang, Hyun Pyo Kim. 1998. Amentoflavone, a Plant biflavone : A New Poteintial Anti-inflammatory Agent. Arch. Pharm. Res. Vol. 4, 406-410
  4. Hyun Sun Lee, Won Keun Oh, Bo Yeon Kim, Soon Cheol Ahn, Dae Ook Kang, et al., 1996. Inhibition of Phospholipase C$\gamma$1 Activity by Amentoflavone isolated from Selaginella tarmariscina. Planta Medica 62, 293-296 https://doi.org/10.1055/s-2006-957887
  5. Ihn rhan Lee et al., 1992 Cytotoxicity of folklorie medicine in murine and human cancer cells. Kor. J. Pharmacogn. 23(3), 132-136
  6. John A, Manthey et al., 1999. Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-$\alpha$ expression by human monocytes. J. Nat. Prod. 62, 441-444 https://doi.org/10.1021/np980431j
  7. J.M. Ray and W.G. Stevenson. 1994. The role of matrix metalloproteinases and their inhibitors in tumor invasion, metastasis and angiogenesis. Eur Respir J. 7, 2062-2072
  8. Kyong-joo Cho, Chang-hyun Yun, Do-young Yoon., 2000. Effect of Biflavonoids extracted from the Bark of Pinus maritima on proinflammatory cytokine lnterleukin-l production in Lipopolysaccharide-stimulated RAW 264.7. Toxicology and Applied Pharmacology 168, 64-71 https://doi.org/10.1006/taap.2000.9001
  9. Linda L., Johnson, Richard Dyer, Donald J, Hupe. 1998. Matrix metalloproteinases. Chem. Biol. 2, 466-471
  10. Min wang et al., 1998. Blocking of collagenase secreation by Estramustin during in vitro tumor cell invasion. Cancer Res. 48, 6262-6271. Nov. 15
  11. Marta L. Corcorn et al., 1996. MMP-2 ; Expression, Activation and Inhibition Enzyme. Protein; 49, 7-19 https://doi.org/10.1002/prot.10198
  12. Moon-Taek Park, Hee-Jae Cha, Joo-Won Jeong, Shin-II Kim, Hae-Young Chung, Nam Deuk Kim. 1999. Glucocorticoid receptor- induced Down-regulation of MMP-9 by Ginseng components, PD and PT contributes to inhibition of the Invasive Capacity of HT1080 Human fibrosarcoma cells. J. Mol. Cells vol 9, 476-483
  13. Peter D Brown. 1997. Matrix metalloproteinases inhibitors. Angiogenesis 1, 142-154 https://doi.org/10.1023/A:1018373520193
  14. Sam Sik Kang, Ju Sun Kim et al., 1990. FIavonoids from the Leaves of Ginkgo biloba. Kor. J. Pharmacogn 21(2), 111-120
  15. Sang-oh Yoon, Moon-moo Kim, An-sik Chung. 2001. Inhibitory Effect of Selenite on Invasion of HT1080 Tumor cells. J. Bio Chem. 276(23), 20085-20092 .june 8 https://doi.org/10.1074/jbc.M101143200
  16. Solomon Habtemariam. 1999. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumar necrosis factor-$\alpha$ in L-929 tumor cells J. Nat. Prod. 60, 775-778 https://doi.org/10.1021/np960581z
  17. Stetler-Stevenson, W. G. et al., Matrix metalloproteinases and tumor invasion; from correlation and causality to the clinic. Semin. Cancer Biol. 7, 147-154 https://doi.org/10.1006/scbi.1996.0020
  18. Steven D shapiro. 1998. Matrix metalloproteinase degradation of extracellular matrix ; biological consrquences., Cell biol. 10, 602-608