Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Bee Venom Inhibits Angiogenesis by Decreasing HIF-1α Expression in HCT116 Cells

봉독의 HIF-1α 발현감소를 통한 혈관신생 억제효과

  • Shin, Jae-Moon (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Jeong, Yun-Jeong (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Park, Kwan-Kyu (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Choe, Jung-Yoon (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Han, Sang-Mi (Department of Agricultural Biology, National Institute of Agricultural Science and Technology) ;
  • Lee, Kwang-Gill (Department of Agricultural Biology, National Institute of Agricultural Science and Technology) ;
  • Yeo, Joo-Hong (Department of Agricultural Biology, National Institute of Agricultural Science and Technology) ;
  • Chung, Il-Kyung (Department of Biotechnology, Catholic University of Daegu) ;
  • Chang, Young-Chae (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine)
  • 신재문 (대구가톨릭대학교 의용생체공학연구소) ;
  • 정윤정 (대구가톨릭대학교 의용생체공학연구소) ;
  • 박관규 (대구가톨릭대학교 의용생체공학연구소) ;
  • 최정윤 (대구가톨릭대학교 의용생체공학연구소) ;
  • 한상미 (농촌진흥청 국립농업과학원) ;
  • 이광길 (농촌진흥청 국립농업과학원) ;
  • 여주홍 (농촌진흥청 국립농업과학원) ;
  • 정일경 (대구가톨릭대학교 자연대학 생명공학과) ;
  • 장영채 (대구가톨릭대학교 의용생체공학연구소)
  • Received : 2011.10.10
  • Accepted : 2012.01.09
  • Published : 2012.01.30
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Abstract

Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

봉독은 동양의학에서 관절염, 류마티즘 및 각종 암을 포함하여 다양한 질병을 치료하기 위하여 이용되었다. 최근 봉독의 신생혈관 억제효과에 대한 연구가 보고되었으나 정확한 분자메커니즘에 대해서는 보고가 미흡하다. 따라서, 본 연구는 봉독이 인간결장암세포인 HCT116세포에서 신생혈관생성과 종양진행에 중요한 역할을 하는 HIF-$1{\alpha}$와 VEGF 발현 억제효과를 조사하였다. 그 결과 봉독은 $CoCl_2$로 유도한 저산소 상태에서 VEGF와, HIF-$1{\alpha}$의 발현을 감소시키며 HIF-$1{\alpha}$의 promoter 영역인 HRE 활성을 억제하였다. 이러한 봉독의 HIF-$1{\alpha}$ 발현억제효과는 ERK1/2의 인산화 조절을 통한 것이며, 봉독은 p38, JNK, AKT의 인산화에는 영향을 끼치지 않았다. 또한 봉독의 효과를 나타내는 단일물질 탐색을 위해 봉독의 생리활성 물질로 알려진 아파민과 멜리틴을 조사한 결과, HIF-$1{\alpha}$와 VEGF 억제효과는 아파민에 기인하는 것이라고 예상 할 수 있었다. 이와 같은 결과를 통하여 본 연구에서는 봉독의 혈관신생 억제에 대한 새로운 신호전달기전 및 인간 결장암세포 전이 억제제로서의 잠재성을 확인하였다.

Keywords

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