Abstract：
We previously reported that the bismuth(III) dithiocarbamate derivative, bismuth diethyldithiocarbamate (1) exhibited greater cytotoxicity while inducing apoptosis via the intrinsic pathway in MCF-7 cells. We further evaluated the other bismuth(III) dithiocarbamate derivatives, Bi[S2CNR]3, with R = (CH2CH2OH)(iPr), (CH2)4, and (CH2CH2OH)(CH3), denoted as 2, 3, and 4, respectively, in the same MCF-7 cell line. 2-4 were found to exhibit IC50 values of 10.33 ± 0.06 µM, 1.07 ± 0.01 µM and 25.37 ± 0.12 µM, respectively, compared to that of cisplatin at 30.53 ± 0.23 µM. Apoptotic promotion via the mitochondrial-dependent pathway was due to the elevation of intracellular reactive oxygen species (ROS), promotion of caspases, release of cytochrome c, fragmentation of DNA, and results of staining assay observed in all compound-treated cells. 2-4 are also capable of suppressing MCF-7 cell invasion and modulate Lys-48 also Lys-63 linked polyubiquitination, leading to proteasomal degradation. Analysis of gene expression via qRT-PCR revealed their modulation, which supported all activities conducted upon treatment with 2-4. Altogether, bismuth dithiocarbamate derivatives, with bismuth(III) as the metal center bound to ligands, isopropyl ethanol, pyrrolidine, and methyl ethanol dithiocarbamate, are potential anti-breast cancer agents that induce apoptosis and suppress metastasis. Further studies using other breast cancer cell lines and in vivo studies are recommended to clarify the anticancer effects of these compounds.
摘要：
我们先前报道了二硫代氨基甲酸铋（III）衍生物，二乙基二硫代氨基甲酸铋（1）表现出更大的细胞毒性，同时通过内在途径诱导MCF-7细胞凋亡。我们进一步评估了其他二硫代氨基甲酸铋（III）衍生物，Bi[S2CNR]3,R=(CH2CH2OH)(iPr),（CH2）4和（CH2CH2OH）（CH3），分别表示为2、3和4，在相同的MCF-7细胞系中。发现2-4的IC50值为10.33±0.06µM，1.07±0.01µM和25.37±0.12µM，分别,与30.53±0.23µM的顺铂相比。通过线粒体依赖性途径促进细胞凋亡是由于细胞内活性氧（ROS）的升高，半胱天冬酶的推广，细胞色素c的释放，DNA片段化,以及在所有化合物处理的细胞中观察到的染色测定结果。2-4还能够抑制MCF-7细胞侵袭并调节Lys-48以及Lys-63连接的聚泛素化，导致蛋白酶体退化。通过qRT-PCR分析基因表达揭示了它们的调节作用，支持2-4治疗后进行的所有活动。总之,二硫代氨基甲酸铋衍生物，以铋（III）作为与配体结合的金属中心，异丙醇,吡咯烷,和乙醇二硫代氨基甲酸甲酯，是诱导细胞凋亡和抑制转移的潜在抗乳腺癌药物。建议使用其他乳腺癌细胞系和体内研究进行进一步研究，以阐明这些化合物的抗癌作用。
