6 TRAILシグナルを介してがん選択的にアポトーシスを誘導する天然物の探索(口頭発表の部)
書誌事項
- タイトル別名
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- Search for Bioactive Natural Products Targeting TRAIL Signaling for Tumor-selective Apoptosis Inducement
抄録
TRAIL (Tumor ecrosis factor (TNF)-related apoptosis-inducing ligand) has emerged as an attrtactive anticaner molecule, because it can cause tomor-selective apoptosis. TRAIL is known to bind to death receptors, such as DR5 (death receptor 5), resulting in the activation of TRAIL signaling and leadint to tumor-selective apoptosis. However, it has become a problem that a number of cancer cells are resistant to TRAIL. Therefore, the activation of TRAIL pathway is very importan in drug discovery. In our search of bioactive antural products, we screened plant extracts collected in Thailand and Bangladesh by DR5 promoter activity assay and TRAIL overcoming activity assay for TRAiL signaling activators. DR5 promoter activity-guided fractionation of the extracts of Combretum quadrangulare (leaf) and Euphorbia neriifolia (lear) led to the isolation of sixteen new cycloartane triterpenes (1-9, 11-17) and a new ingol diterpene (18). Especially, 16 and 18 (2.2μM) enhanced DR5 expression 7.5 and 4.1-fold, respectively. TRAIL-resistance overcoming activity-quided fractionation of the extracts of Sida acuta (whole plants) and Amoora cucullata (leaf) led to the isolation of four new compound (21, 24-26) and several known compounds. Among them, 22 showed the most potent activity (IC_<50> with 100 ng/mL of TRAIL: 1.3 nM, IC_<50> without TRAIL: 18.8 nM). Compound 22 enhanced TRAIL-induced apoptosis through the activation of caspase-3/7, augmenting the expression of DR4 and DR5 in AGS cells.
収録刊行物
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- 天然有機化合物討論会講演要旨集
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天然有機化合物討論会講演要旨集 52 (0), 31-36, 2010
天然有機化合物討論会実行委員会
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詳細情報 詳細情報について
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- CRID
- 1390001206077551744
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- NII論文ID
- 110009757730
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- ISSN
- 24331856
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可