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A bismuth diethyldithiocarbamate compound induced apoptosis via mitochondria-dependent pathway and suppressed invasion in MCF-7 breast cancer cells
Biometals ( IF 3.5 ) Pub Date : 2021-02-08 , DOI: 10.1007/s10534-021-00286-0
Pit Foong Chan 1 , Kok Pian Ang 1 , Roslida Abd Hamid 1
Affiliation  

Interest in bismuth(III) dithiocarbamate complexes as potential drug candidates is increasing due to their low toxicity compared to other group 15 elements (pnictogen) of the periodic table. Bismuth dithiocarbamate compounds have been reported to induce greater cytotoxicity in various human carcinoma cancer cell lines. Using various in vitro cancer-related assays, we investigated the antiproliferative activity of bismuth diethyldithiocarbamate, denoted as 1, against the MCF-7 human breast adenocarcinoma cell line and the effect on genes that may be involved in antiproliferation, apoptosis, DNA fragmentation, invasion and polyubiquitination functions. In general, 1 exhibited high cytotoxicity in MCF-7 cells, with an IC50 of 1.26 ± 0.02 µM, by inducing the intrinsic apoptotic pathway, as ascertained by measurements of intracellular reactive oxygen species (ROS), caspase activity, the amount of cytochrome c released and the extent of DNA fragmentation and by staining assays that reveal apoptotic cells. In addition, 1 significantly attenuated cell invasion and modulated several cancer-related genes, including PLK2, FIGF, FLT4, PARP4, and HDAC11, as determined via gene expression analysis. The NF-κB signaling pathway was inhibited by 1 upon the activation of Lys48- and Lys63-linked polyubiquitination, thus leading to its degradation via the proteasome. Overall, 1 has the potential to act as an antiproliferative agent and a proteasome inhibitor in estrogen-positive breast cancer.



中文翻译:

二乙基二硫代氨基甲酸铋化合物通过线粒体依赖性途径诱导细胞凋亡并抑制 MCF-7 乳腺癌细胞的侵袭

由于与元素周期表中的其他 15 族元素(pnictogen)相比毒性低,人们对二硫代氨基甲酸铋 (III) 复合物作为潜在候选药物的兴趣正在增加。据报道,二硫代氨基甲酸铋化合物在各种人类癌细胞系中诱导更大的细胞毒性。使用各种体外癌症相关测定,我们研究了二乙基二硫代氨基甲酸铋(表示为1)对 MCF-7 人乳腺癌细胞系的抗增殖活性以及对可能参与抗增殖、细胞凋亡、DNA 片段化、侵袭的基因的影响和多泛素化功能。一般来说,1在 MCF-7 细胞中表现出高细胞毒性,IC 501.26 ± 0.02 µM,通过诱导内在凋亡途径,通过测量细胞内活性氧 (ROS)、半胱天冬酶活性、释放的细胞色素c的量和 DNA 碎片的程度以及通过染色分析显示凋亡细胞来确定。此外,通过基因表达分析确定,1显着减弱细胞侵袭并调节多种癌症相关基因,包括PLK2、FIGF、FLT4、PARP4HDAC11。NF-κB 信号通路在 Lys48 和 Lys63 连接的多泛素化激活后被1抑制,从而导致其通过蛋白酶体降解。总的来说,1 具有在雌激素阳性乳腺癌中作为抗增殖剂和蛋白酶体抑制剂的潜力。

更新日期:2021-02-08
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