The toxin component of targeted anti‐tumor toxins determines their efficacy increase by saponins
The toxin component of targeted anti‐tumor toxins determines their efficacy increase by saponins
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靶向抗肿瘤毒素的毒素成分决定了皂苷提高其功效
DOI：
10.1016/j.molonc.2012.01.004
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发表时间：
2012
影响因子：
6.6
通讯作者：
H. Fuchs
中科院分区：
文献类型：
--
作者：
A. Weng;M. Thakur;F. Beceren-Braun;D. Bachran;C. Bachran;S.B. Riese;K. Jenett-Siems;R. Gilabert-Oriol;M.F. Melzig;H. Fuchs
肿瘤靶向蛋白毒素是由一种毒性酶偶联到一个特定的细胞结合域，靶向癌症相关抗原组成的。靶向毒素的抗肿瘤治疗伴随着剂量限制的副作用。靶向毒素用于人类治疗的未来前景将取决于减少副作用。某些植物次生代谢物（皂苷）被证明可以增加特定表皮生长因子受体（EGFR）靶向毒素的功效，同时副作用也大大减少。本研究旨在研究替换融合到EGF配体结合域的不同毒素片段对皂苷增强能力的影响，以对抗针对EGFR的不同抗肿瘤毒素的皂苷介导的疗效增加的治疗潜力。我们设计了几种不同毒性部分的EGFR靶向毒素。我们将每一种靶向毒素与从观赏植物Gypsophila paniculata L.中分离出来的纯化皂苷（SA1641）联合使用，对SA1641进行了表征，并研究了SA1641介导的对EGFR转染的NIH - 3T3细胞的功效提高。我们观察到SA1641介导的效力增加高度依赖于用于构建目标毒素的毒素的性质，表明高特异性。结构比对显示皂苷和dianthin‐30之间具有高度同源性，这两个毒性部分在与SA1641结合后获益最多。我们进一步证明SA1641不影响质膜通透性，表明SA1641与目标毒素的毒素成分在细胞内相互作用。表面等离子体共振测量表明SA1641与目标毒素的毒素成分有短暂的结合。
Tumor‐targeting protein toxins are composed of a toxic enzyme coupled to a specific cell binding domain that targets cancer‐associated antigens. The anti‐tumor treatment by targeted toxins is accompanied by dose‐limiting side effects. The future prospects of targeted toxins for therapeutic use in humans will be determined by reduce side effects. Certain plant secondary metabolites (saponins) were shown to increase the efficacy of a particular epidermal growth factor receptor (EGFR)‐targeted toxin, paralleled by a tremendous decrease of side effects.This study was conducted in order to investigate the effects of substituting different toxin moieties fused to an EGF ligand binding domain on the augmentative ability of saponins for each against therapeutic potential of the saponin‐mediated efficacy increase for different anti‐tumor toxins targeting the EGFR.We designed several EGFR‐targeted toxins varying in the toxic moiety. Each targeted toxin was used in combination with a purified saponin (SA1641), isolated from the ornamental plant Gypsophila paniculata L. SA1641 was characterized and the SA1641‐mediated efficacy increase was investigated on EGFR‐transfected NIH‐3T3 cells.We observed a high dependency of the SA1641‐mediated efficacy increase on the nature of toxin used for the construction of the targeted toxin, indicating high specificity.Structural alignments revealed a high homology between saporin and dianthin‐30, the two toxic moieties that benefit most from the combination with SA1641.We further demonstrate that SA1641 did not influence the plasma membrane permeability, indicating an intracellular interaction of SA1641 and the toxin components of targeted toxins. Surface plasmon resonance measurements point to a transient binding of SA1641 to the toxin components of targeted toxins.
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一种简单的满天星皂苷分离方法，用于靶向毒素和皂苷在肿瘤治疗中的联合应用
影响因子：
2.7
作者：
Alexander Weng1;Diana Bachran2;Cornelia Görick1;Christopher Bachran2;Hendrik Fuchs2;Matthias Melzig1
通讯作者：
Matthias Melzig1
影响因子：
6.4
作者：
Heisler, I;Keller, J;Fuchs, H
通讯作者：
Fuchs, H
肿瘤治疗中皂苷分离的便捷方法。
DOI：
--
发表时间：
2010
期刊：
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
影响因子：
--
作者：
A. Weng;K. Jenett‐Siems;P. Schmieder;D. Bachran;C. Bachran;C. Görick;M. Thakur;H. Fuchs;M. Melzig
通讯作者：
M. Melzig
影响因子：
9.3
作者：
Bachran, Christopher;Sutherland, Mark;Fuchs, Hendrik
通讯作者：
Fuchs, Hendrik
影响因子：
2.2
作者：
MOSMANN, T
通讯作者：
MOSMANN, T