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국 문 초 록
이소람네틴에 의한 HIF-1a 억제 효능 연구
서 수 호
지 도 교 수 : 신 상 미 약학과
조선대학교 대학원
이소람네틴은 미나리에서 추출한 플라보노이드 구조를 갖는 성분이다. 기존 연구를 통해 이소람네틴의 항산화, 항염증 및 항암 활성 등의 긍정적인 효능이 보고되었다. 본 연구에서는 대장암 세포에서 이소람네틴의 항산화 효과가 암을 억제하는데 기여할 수 있는지 조사하였다. 이소람네틴은 HCT116 과 HT29 세포에서 저산소증 또는 CoCl2 로 유도한 hypoxia inducible factor-1a (HIF-1a)의 축적을 억제하였다. 또한, CoCl2로 유도한 hypoxia response element (HRE) 리포터 유전자의 활성을 억제하였다. 저산소상태에서 이소람네틴의 HIF-1a 억제는 glucose transporter1 (GLUT1), lactate dehydrogenase A (LDH A), carbonic anhydrase-IX (CA-IX) 및 pyruvate dehydrogenase kinase1 (PDK1) 와 같은 HIF-1a 타겟 유전자 억제로 이어졌다.
이소람네틴은 HIF-1a 단백질 안정성을 감소시키는 것으로 관찰되었으나, HIF-1a 유비퀴틴화는 변화시키지 않았다. 이에 다음으로 HIF-1a의 억제에 이소람네틴의 항산화 효과가 연관성이 있는지 평가하였다. 이소람네틴은 CoCl2 또는 H2O2 로