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选择的钒和钼有机金属配合物在人白血病 T 细胞中的抗肿瘤作用研究。

Study of antitumor effect of selected vanadium and molybdenum organometallic complexes in human leukemic T-cells.

机构信息

Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.

Department of Biological and Biochemical Science, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.

出版信息

Chem Biol Interact. 2015 Dec 5;242:61-70. doi: 10.1016/j.cbi.2015.09.017. Epub 2015 Sep 25.

Abstract

This work describes cytotoxic effect of non-platinum metal-based compounds on the human T-leukemic cells with different p53 status (p53 wild-type MOLT-4 and p53-deficient Jurkat cells). The cytotoxic and apoptosis-inducing effect of the vanadium complex [(η(5)-C5H5)2V(5-NH2-phen)]OTf (V1) and molybdenum complex [(η(3)-C3H5)Mo(CO)2(phen)Cl] (Mo1) were studied using flow cytometry, spectrophotometry and Western blotting. We found that the cytotoxic effect of both tested complexes after 24 h is higher against the both examined cell lines than that of cis-platin (cis-DDP). At later investigated time intervals of 48 and 72 h, the cytotoxic effect of the cis-DDP increased but the values of the cytotoxicity of the tested V1 and Mo1 complexes remained unchanged, with the cytotoxicity of V1 comparable to that of cis-DDP. Furthermore we observed that the apoptotic process was induced by the activation of the caspases 9 (intrinsic pathway) and 8 (extrinsic pathway) in cells exposed to evaluated complexes. In case of the p53 wild-type MOLT-4 cells, the expression of the tumor-suppressor protein p53 and its form phosphorylated at the serine 15 increased after both V1 and Mo1 treatment, similar to the effect of cis-DDP.

摘要

这项工作描述了非铂类金属基化合物对具有不同 p53 状态(p53 野生型 MOLT-4 和 p53 缺失型 Jurkat 细胞)的人 T 白血病细胞的细胞毒性作用。使用流式细胞术、分光光度法和 Western blot 研究了钒配合物[(η(5)-C5H5)2V(5-NH2-phen)]OTf(V1)和钼配合物(η(3)-C3H5)Mo(CO)2(phen)Cl对细胞的细胞毒性和诱导凋亡作用。我们发现,两种测试配合物在 24 小时后对两种被检测细胞系的细胞毒性作用均高于顺铂(cis-DDP)。在随后研究的 48 小时和 72 小时时间间隔内,cis-DDP 的细胞毒性作用增加,但测试的 V1 和 Mo1 配合物的细胞毒性值保持不变,V1 的细胞毒性与 cis-DDP 相当。此外,我们观察到,暴露于评估配合物的细胞中,凋亡过程是由半胱天冬酶 9(内在途径)和 8(外在途径)的激活诱导的。在 p53 野生型 MOLT-4 细胞中,V1 和 Mo1 处理后肿瘤抑制蛋白 p53及其丝氨酸 15 磷酸化形式的表达增加,与 cis-DDP 的作用相似。

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