一种基于HER2/neu特异性亲环素蛋白和光活性黄素蛋白miniSOG的新型抗癌毒素。
A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG.
作者信息
Proshkina G M, Shilova O N, Ryabova A V, Stremovskiy O A, Deyev S M
机构信息
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St, 16/10, Moscow 117997, Russia.
Prokhorov General Physics Institute, Russian Academy of Sciences, Vavilova St, 38, 119991 Moscow, Russia; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Kashirskoe Highway, 31, Moscow 115409, Russia.
出版信息
Biochimie. 2015 Nov;118:116-22. doi: 10.1016/j.biochi.2015.08.013. Epub 2015 Aug 28.
Cytotoxic effects of a new targeted phototoxin DARPin-miniSOG and mechanism of its action were investigated in vitro. It was determined that DARPin-miniSOG causes light-induced death of HER2/neu-positive cancer cells (IC50 0.8 μM). Treatment of the cells with DARPin-miniSOG in the presence of ascorbic acid eliminated the light-induced cytotoxic action of the protein. This observation suggests the involvement of oxidative stress in the mechanism of the phototoxin action. DNA fragmentation analysis, caspase-3 activity assay and PI-staining of HER2/neu-positive cancer cells treated with DARPin-miniSOG indicated that phototoxin induces necrotic cell death under blue light illumination. Co-localization analysis showed that DARPin-miniSOG accumulates mostly in endosomes and lysosomes.
在体外研究了新型靶向光毒素DARPin-miniSOG的细胞毒性作用及其作用机制。已确定DARPin-miniSOG可导致HER2/neu阳性癌细胞的光诱导死亡（IC50为0.8μM）。在抗坏血酸存在的情况下，用DARPin-miniSOG处理细胞消除了该蛋白的光诱导细胞毒性作用。这一观察结果表明氧化应激参与了光毒素的作用机制。对用DARPin-miniSOG处理的HER2/neu阳性癌细胞进行DNA片段化分析、半胱天冬酶-3活性测定和PI染色表明，光毒素在蓝光照射下诱导坏死性细胞死亡。共定位分析表明，DARPin-miniSOG主要积聚在内体和溶酶体中。
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