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Antiangiogenic activity of non-aqueous fraction from Sparassis crispa extract in human umbilical vein endothelial cells

혈관내피세포에서 꽃송이버섯(Sparassis crispa) 소수성 추출물의 항혈관신생 활성

  • Han, Jang Mi (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University) ;
  • Gong, So Youn (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University) ;
  • Sohng, Jae Kyung (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University) ;
  • Kang, Yue Jai (Department of Aquatic Life and Medical Sciences, Sun Moon University) ;
  • Jung, Hye Jin (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University)
  • 한장미 (선문대학교 제약생명공학과) ;
  • 공소연 (선문대학교 제약생명공학과) ;
  • 송재경 (선문대학교 제약생명공학과) ;
  • 강예재 (선문대학교 수산생명의학과) ;
  • 정혜진 (선문대학교 제약생명공학과)
  • Received : 2019.01.01
  • Accepted : 2019.02.08
  • Published : 2019.04.30

Abstract

Sparassis crispa is an edible mushroom that is distributed in Korea, Japan, Europe, and North America. It exerts various biological activities such as immunopotentiation, anti-diabetic, anti-cancer, and anti-inflammatory effects. Recently, we separated the health functional non-aqueous fraction from the chloroform extract of S. crispa (SCF4). In this study, we evaluated the antiangiogenic activity of SCF4 in human umbilical vein endothelial cells (HUVECs). SCF4 effectively inhibited vascular endothelial growth factor (VEGF)-induced cell growth at concentrations ($5-25{\mu}g/mL$) showing no cytotoxic effects. SCF4 inhibited VEGF-induced invasiveness and tube formation ability, which are in vitro angiogenic features of HUVECs, in a dose-dependent manner. In addition, SCF4 markedly suppressed in vivo angiogenesis of chorioallantoic membrane from growing chick embryos without cytotoxicity. Furthermore, SCF4 downregulated the phosphorylation of VEGFR2, AKT, and ERK1/2, which are major angiogenic signal mediators. These results suggest that SCF4 inhibited angiogenesis by suppressing the VEGFR2 signaling pathways without cytotoxicity.

본 연구에서는 꽃송이버섯 소수성 추출물(SCF4)의 항혈관신생활성을 혈관내피세포인 HUVECs을 사용하여 확인하였다. 그 결과, SCF4는 세포 독성을 나타내지 않는 $5-25{\mu}g/mL$의 농도에서 VEGF에 의해 유도된 혈관내피세포 증식을 유의적으로 감소시켰을 뿐만 아니라, 혈관내피세포 침윤성과 관 형성 능력을 농도의 존적으로 감소시켜 in vitro 혈관신생을 효과적으로 저해함을 확인하였다. 또한, SCF4는 독성을 나타내지 않고 CAM의 혈관신생을 저해함으로써, in vivo 혈관신생을 효과적으로 저해함을 확인하였다. 마지막으로 SCF4가 혈관신생을 유도하는 주요 신호전달 경로인 VEGFR2, AKT 및 ERK1/2의 전체 단백질 발현 수준의 변화없이 인산화를 저해함을 확인하였다. 따라서, 본 연구는 꽃송이버섯 소수성 추출물이 혈관신생 저해활성을 나타내고 이러한 현상은 VEGFR2 신호전달경로의 억제를 통해 진행됨을 입증하여, 혈관신생 관련 질환 예방 및 치료를 위한 천연물 소재로서의 적용 가능성을 새롭게 제시하였다.

Keywords

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Fig. 1. The antiproliferative activity of SCF4 on HUVECs.

SPGHB5_2019_v51n2_141_f0002.png 이미지

Fig. 2. The effect of SCF4 on angiogenesis in vitro.

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Fig. 3. The effect of SCF4 on angiogenesis in vivo.

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Fig. 4. The effect of SCF4 on VEGFR2-dependent signal transduction in HUVECs.

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