Targeting the disturbed redox equilibrium in chronic lymphocytic leukemia by novel reactive oxygen species-catalytic ‘sensor/effector’ compounds
Targeting the disturbed redox equilibrium in chronic lymphocytic leukemia by novel reactive oxygen species-catalytic ‘sensor/effector’ compounds
复制标题
通过新型活性氧催化“传感器/效应器”化合物来靶向慢性淋巴细胞白血病中扰乱的氧化还原平衡
DOI：
10.3109/10428194.2011.568077
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发表时间：
2011
影响因子：
2.6
通讯作者：
M. Herling
中科院分区：
文献类型：
--
作者：
Nils Lilienthal;C. Prinz;A. Peer;Mandy Doering;L. A. Ba;M. Hallek;C. Jacob;M. Herling
前体转化、克隆维持和癌症的治疗抗性显著地由解除调节的活性氧（ROS）介导，其主要充当DNA应激物。在这里，我们证明，在慢性淋巴细胞白血病（CLL）的ROS升高可能是一个有前途的治疗目标。我们设计了有机硫属元素，其基于“传感器/效应器”原理，将通过优先在CLL细胞中产生不可耐受的高ROS水平来赋予选择性细胞毒性，因为这些具有高水平的氧化还原负担。我们的新化合物显示出令人鼓舞的概况，有效诱导细胞凋亡，低正常细胞毒性，和有前途的化疗协同作用。这些发现保证了对CLL中的这种治疗原则的进一步机制和临床前研究。
Precursor transformation, clonal sustenance, and therapeutic resistance in cancer are significantly mediated by deregulated reactive oxygen species (ROS), which primarily act as DNA-stressors. Here, we demonstrate that elevated ROS in chronic lymphocytic leukemia (CLL) may represent a promising therapeutic target. We designed organochalcogens, which, based on a ‘sensor/effector’ principle, would confer selective cytotoxicity through the generation of intolerably high ROS levels preferentially in CLL cells, as these carry a high-level redox burden. Our novel compounds show an encouraging profile of efficient induction of apoptosis, low normal cell toxicity, and promising chemotherapy synergism. These findings warrant further mechanistic and preclinical studies of this therapeutic principle in CLL.
影响因子：
168.9
作者：
Hallek, M.;Fischer, K.;Stilgenbauer, S.
通讯作者：
Stilgenbauer, S.
影响因子：
20.3
作者：
Trachootham, Dunyaporn;Zhang, Hui;Huang, Peng
通讯作者：
Huang, Peng