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TRAIL에 저항성을 가진 간암세포에 Sulforaphan과 TRAIL 의 병합 처리 시 apoptosis촉진 효과 및 조절 기전 분석 : Sulforaphane 에 의한 반응성 산소종 생성과 DR5 발현 유도의 중요성 분석
- Alternative Title
- KIM HEESUE
- Author(s)
- 김희수
- Alternative Author(s)
- KIM HEESUE
- Advisor
- 최경숙
- Department
- 일반대학원 의학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2006-02
- Language
- eng
- Alternative Abstract
- Sulforaphane (SFN) is a chemopreventive agent present in various cruciferous vegetables, including broccoli. Here, we show that treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with subtoxic doses of SFN significantly induces rapid apoptosis in TRAIL-resistant hepatoma cells. Neither TNF-α- nor Fas-mediated apoptosis was sensitized in hepatoma cells by cotreatment with SFN, suggesting that SFN can selectively sensitize cells to TRAIL-induced apoptosis but not to apoptosis mediated by other death receptors. We found that SFN treatment significantly upregulated mRNA and protein levels of DR5, a death receptor of TRAIL. This was accompanied by an increase in the generation of reactive oxygen species. Pretreatment with N-acetylcysteine and overexpression of catalase inhibited SFN-induced upregulation of DR5 and almost completely blocked the cotreatment-induced apoptosis. Furthermore, the SFN-mediated sensitization to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs for DR5. These results collectively indicate that SFN-induced generation of reactive oxygen species and the subsequent upregulation of DR5 are critical for triggering and amplifying TRAIL-induced apoptotic signaling. We also found that SFN can sensitize both Bcl-xL- and Bcl-2-overexpressing hepatoma cells to TRAIL-induced apoptosis, indicating that treatment with a combination of TRAIL and SFN may be a safe strategy for treating resistant hepatomas.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Medicine > 3. Theses(Master)
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