Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
J Phys Chem B. 2010 Mar 18;114(10):3639-47. doi: 10.1021/jp909143b.
A water-soluble Pd(II) complex (2,2'-bipyridinglycinato Pd(II) nitrate) has been synthesized and characterized. The effect of synthesized complex on the carrier model protein structure and cell proliferation was investigated. Whey carrier protein beta-lactoglobulin-B (BLG-B) and chronic myelogenous leukemia cell line K562 were the targets. Fluorescence and CD instruments were used to assess effect of the complex on the protein structure at different temperatures. Growth inhibitory and apoptotic effect of the Pd(II) complex toward the cancer cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. This complex exhibited potent cytotoxic properties against chronic myelogenous leukemia cell line K562. The cells showed different sensitivity to complex. Cytotoxic studies shown that Pd(II) complex induced apoptosis of K562 cells in a concentration and time dependent manner. Then, it might be concluded that Pd(II) complex is a promising antiproliferative agent and should execute its biological effects by inducing apoptosis. Results of fluorescence studies revealed that Pd(II) complex can quench the intrinsic fluorescence emission of the protein at different temperatures. The far- and near-UV CD studies displayed that the Pd(II) complex induces changes in the secondary and tertiary structures of BLG-B at different temperatures. The biological significance of this work is evident since BLG serves as a carrier molecule for several antitumor compounds. Therefore, the interaction of the Pd(II) complex (with antitumor activity) can provide useful information to better design metal anticancer complexes with fewer side effects.
一种水溶性的 Pd(II) 配合物（2,2'-联吡啶甘氨酸合 Pd(II) 硝酸盐）已被合成并进行了表征。研究了合成配合物对载体模型蛋白结构和细胞增殖的影响。乳清载体蛋白β-乳球蛋白-B（BLG-B）和慢性髓系白血病细胞系 K562 是研究的对象。荧光和 CD 仪器用于评估不同温度下配合物对蛋白质结构的影响。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法和流式细胞术测定了该 Pd(II) 配合物对癌细胞的生长抑制和凋亡作用。该配合物对慢性髓系白血病细胞系 K562 表现出很强的细胞毒性。细胞对该配合物的敏感性不同。细胞毒性研究表明，Pd(II) 配合物以浓度和时间依赖的方式诱导 K562 细胞凋亡。因此，可以得出结论，Pd(II) 配合物是一种很有前途的抗增殖剂，应该通过诱导细胞凋亡来发挥其生物学作用。荧光研究结果表明，Pd(II) 配合物可以在不同温度下猝灭蛋白质的固有荧光发射。远紫外和近紫外 CD 研究显示，Pd(II) 配合物在不同温度下诱导 BLG-B 的二级和三级结构发生变化。这项工作的生物学意义是显而易见的，因为 BLG 是几种抗肿瘤化合物的载体分子。因此，Pd(II) 配合物（具有抗肿瘤活性）的相互作用可以为设计副作用更小的金属抗癌配合物提供有用的信息。
