Química-Física Molecular, Departamento de Química, FCTUC, Universidade de Coimbra, Portugal.
Chem Biol Drug Des. 2011 Jun;77(6):477-88. doi: 10.1111/j.1747-0285.2011.01081.x. Epub 2011 Apr 1.
A dinuclear palladium-based complex (Pd(2) -Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd(2) -Spm is more effective against the estrogen receptors [ER(-)] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cell line. It was shown that, like cDDP, Pd(2) -Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd(2) -Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd(2) -Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd(2) -Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated.
合成了一种双核钯基配合物（Pd(2)-Spm），并将其与顺铂（cDDP）在两种不同的人乳腺癌细胞系（MCF-7 和 MDA-MB-231）以及未转化的细胞系（BJ 成纤维细胞）上进行了比较。结果表明，Pd(2)-Spm 对雌激素受体 [ER(-)] MDA-MB-231 细胞系更有效，而 cDDP 对 ER(+) MCF-7 细胞系显示出更好的效果。结果表明，与 cDDP 一样，Pd(2)-Spm 触发 H2AX 的磷酸化，表明该化合物会损伤 DNA。除了 DNA，Pd(2)-Spm 还靶向细胞骨架，对细胞形态的影响大于 cDDP。在 PI3K 抑制剂wortmannin 的存在下，Pd(2)-Spm 和 cDDP 具有相反的抗增殖活性。此外，Pd(2)-Spm 在优化浓度下显示出快速的抗增殖作用，而 cDDP 似乎具有较慢的动力学。这些结果表明，这两种配合物的作用机制不同，这可能解释了它们在联合给药时的协同作用。
