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Antiangiogenic Activity of Coptis chinensis Franch. Water Extract in in vitro and ex vivo Angiogenesis Models

In vitro와 ex vivo 혈관신생 모델에서 황련 냉수추출물의 신생혈관 억제효과

  • Kim, Eok-Cheon (Division of Biological Science and Technology, College of Science and Technology, Yonsei University) ;
  • Kim, Seo Ho (Division of Biological Science and Technology, College of Science and Technology, Yonsei University) ;
  • Lee, Jin-Ho (Division of Biological Science and Technology, College of Science and Technology, Yonsei University) ;
  • Kim, Tack-Joong (Division of Biological Science and Technology, College of Science and Technology, Yonsei University)
  • 김억천 (연세대학교 과학기술대학 생명과학기술학부) ;
  • 김서호 (연세대학교 과학기술대학 생명과학기술학부) ;
  • 이진호 (연세대학교 과학기술대학 생명과학기술학부) ;
  • 김택중 (연세대학교 과학기술대학 생명과학기술학부)
  • Received : 2016.08.05
  • Accepted : 2017.01.16
  • Published : 2017.01.30

Abstract

Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

혈관신생, 즉 새로운 혈관형성은 종양의 성장과 전이에 중요한 역할을 한다고 알려져 있으며, 암 치료에 중요한 목표물이 되고 있다. 이 연구의 목적은 황련 냉수추출물의 혈관신생 억제작용의 효과를 밝히고 항암제로서의 가능성을 평가하고자 한다. Ex vivo rat aortic ring assay 실험결과 신생혈관성장을 억제하는 결과를 확인하였고, 이것을 통해 황련 냉수추출물이 혈관신생과정의 주요한 단계와 내피세포의 증식, 이동, 침투, 혈관내피세포자극인자에 의한 반응으로 모세관 모양의 관 형성작용을 억제함을 알아내었다. 또한 황련 냉수추출물을 처리하였을 때, 세포주기가 억제되고 VEGF에 의한 반응으로 인해 G0/G1 주기에서 S 주기로 가는 과정을 예방하고, VEGF에 의해 활성화가 유도되는 MMP-2, MMP-9이 감소되었다. 따라서 이들의 결과는 황련 냉수추출물이 종양의 발달 단계 중 혈관신생을 방해하는 잠재적인 항암약물의 소재로 고려될 수 있음을 제안한다.

Keywords

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