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钒(III)与L-半胱氨酸的配合物——稳定性、物种形成及对肝癌Morris 5123细胞中肌动蛋白的影响

Vanadium(III) complexes with L-cysteine--stability, speciation and the effect on actin in hepatoma Morris 5123 cells.

作者信息

Osińska-Królicka I, Podsiadły H, Bukietyńska K, Zemanek-Zboch M, Nowak D, Suchoszek-Łukaniuk K, Malicka-Błaszkiewicz M

机构信息

Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland.

出版信息

J Inorg Biochem. 2004 Dec;98(12):2087-98. doi: 10.1016/j.jinorgbio.2004.09.013.

Abstract

The complexation processes of vanadium(III) with L-cysteinate and s-methyl-L-cysteinate ligands have been studied in aqueous solutions in the pH range 2-7 by the pH-potentiometric, UV-Vis absorption and CD spectroscopy methods. The equilibria model of complex formation, evaluated by SUPERQUAD program, so as careful inspection of spectroscopic data have allowed to determine the speciation and the coordination mode of vanadium(III) ion in the major species present in aqueous solutions. Relatively stable ML2 species of vanadium(III)-L-cysteinate system exists in aqueous solutions above pH 5. It was deduced from spectral data that the coordination sphere of vanadium(III) ion in V(Cys)2 is completed by oxygen, nitrogen and sulfur atoms of two L-cysteinate ligands. Solution of vanadium(III) with L-cysteine (pH approximately 7, L/M=20) was administrated to the culture medium of hepatoma Morris 5123 growing cells. Cytotoxic effect of this solution towards tumor cells was observed. The viability of these cells depended on the complex concentration. It was reduced by 70% at 100 microM of the vanadium species concentration in the culture medium. The death of cancer cells seems to be induced on apoptotic route. The statistically significant increase of total actin level and filamentous to monomeric actin ratios (F/G) were found in the cytoplasm of cells exposed to the vanadium(III)-L-cysteine complex. It was accompanied by the rearrangement of actin cytoskeleton architecture. These factors are important for migration and metastasis formation of the cancer cells.

摘要

通过pH电位滴定法、紫外可见吸收光谱法和圆二色光谱法,研究了钒(III)与L-半胱氨酸和S-甲基-L-半胱氨酸配体在pH值为2至7的水溶液中的络合过程。通过SUPERQUAD程序评估络合物形成的平衡模型,并仔细检查光谱数据,从而确定了水溶液中主要物种中钒(III)离子的形态和配位模式。在pH值高于5的水溶液中存在相对稳定的钒(III)-L-半胱氨酸体系的ML2物种。从光谱数据推断,V(Cys)2中钒(III)离子的配位球由两个L-半胱氨酸配体的氧、氮和硫原子完成。将钒(III)与L-半胱氨酸的溶液(pH约为7,L/M = 20)加入到Morris 5123肝癌生长细胞的培养基中。观察到该溶液对肿瘤细胞的细胞毒性作用。这些细胞的活力取决于络合物浓度。在培养基中钒物种浓度为100 microM时,细胞活力降低了70%。癌细胞的死亡似乎是通过凋亡途径诱导的。在暴露于钒(III)-L-半胱氨酸络合物的细胞细胞质中,发现总肌动蛋白水平以及丝状肌动蛋白与单体肌动蛋白的比率(F/G)有统计学意义的增加。同时伴随着肌动蛋白细胞骨架结构的重排。这些因素对于癌细胞的迁移和转移形成很重要。

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