オスミウム ((VI) ニトリド複合体のバイデント酸リガンドは,細胞内ターゲティングと細胞死経路を制御する
Kogularamanan Suntharalingam1, Timothy C Johnstone, Peter M Bruno
1Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|September 18, 2013
まとめ
抗増殖オスミウム化合物は,調節可能な細胞反応を示します. 複合体4におけるリガンド変異は,がん細胞におけるエンドプラズマ網膜のストレスとp53-独立したアポトーシスを誘発する.
科学分野:
- 無機化学 無機化学とは
- 癌生物学 癌生物学について
- 細胞のストレス反応は,
背景:
- 抗増殖オスミウム (((VI) ニトリド化合物 (OsN (((N^N) Cl3) は,がん治療のために研究されています.
- これらのオスミウム複合体のリガンド改変により,それらの生物学的活性が変化する可能性があります.
研究 の 目的:
- オスミウム (VI) ニトリド化合物の細胞反応を,様々なリガンドで調べる.
- 癌細胞におけるオスミウム化合物の作用機構を理解する.
主な方法:
- 異なるN^Nリガンドを持つオスミウム (VI) ニトリド化合物の合成と特徴付け.
- 細胞検査は,DNAの損傷,細胞サイクル進行,アポトーシスを評価するためのものです.
- p53経路と展開されたタンパク質応答に関連するタンパク質発現の分析.
主要な成果:
- コンプレックス2によるDNA損傷,p53経路の活性化,G2/M細胞サイクル停止,カスパース依存アポトーシス.
- コンプレックス4が誘発したエンドプラズマ網膜 (ER) ストレス,展開タンパク質応答 (UPR) 経路の活性化,およびp53-独立のアポトーシス.
- 化合物4は,がん細胞にERストレスを誘発する最初の報告されたオスミウム化合物です.
結論:
- オスミウム ((VI) ニトリド化合物の微妙なリガンド改変は,細胞の反応を正確に調整することができます.
- オスミウム複合体4は,ERストレス媒介によるアポトシスを誘導することによって,新しい治療戦略を表しています.
- がん治療のためのオスミウムベースの化合物のさらなる研究が必要である.
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