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Vanadocene dichloride inhibits cell proliferation by targeting Aurora B
Metallomics ( IF 2.9 ) Pub Date : 2018-07-13 00:00:00 , DOI: 10.1039/c8mt00089a
Tzu-Chia Ting,Meng-Ya Chang,Tzu-Yen Hsu,Wen-Pin Wang,Yi-Jen Hsieh,Chih-Jui Chang

Vanadocene dichloride (VDC) was shown to exhibit antitumor properties against a wide spectrum of tumor cell lines. Many studies have been carried out to reveal the bioactivities of VDC and the interaction mechanism of VDC with biological molecules in test tubes. One of the bioactivities of VDC is to arrest the cell cycle at the G2/M phase. However, its underlying mechanisms of action and cytotoxicity profile are still not fully understood. HeLa cells were used in this study, and the IC50 value of VDC was 8.61 μM after a 24-hour treatment. We used an immunofluorescence staining method to analyze the morphology of cells in the mitosis stage to elucidate what defects caused cell arrest in mitosis. Chromosomal misalignment was found to be the major phenotype. One of the proteins responsible for chromosome alignment at the metaphase is Aurora B kinase. Results of immunoblotting assay showed that Aurora B kinase activity was inhibited by VDC treatment. More than 50% of the Aurora B activity was inhibited when cells were treated with VDC at a concentration of 6.25 μM. That VDC was able to induce defects in chromosomal alignment at the metaphase by inhibiting the activity of Aurora B kinase is an important mechanism of VDC to be developed as an antitumor agent.

中文翻译:

瓦那多烯二氯化物通过靶向Aurora B抑制细胞增殖

瓦那多烯二氯化物(VDC)已显示出对多种肿瘤细胞系的抗肿瘤特性。已经进行了许多研究以揭示VDC的生物活性以及VDC与试管中的生物分子的相互作用机理。VDC的生物活性之一是将细胞周期停滞在G2 / M期。然而,其潜在的作用机制和细胞毒性概况仍然不完全了解。在这项研究中使用了HeLa细胞,经过24小时处理后,VDC的IC50值为8.61μM。我们使用免疫荧光染色方法分析有丝分裂阶段的细胞形态,以阐明哪些缺陷导致有丝分裂中的细胞停滞。发现染色体错位是主要表型。在中期,负责染色体对齐的蛋白质之一是Aurora B激酶。免疫印迹分析结果表明,VDC处理可抑制Aurora B激酶活性。当用浓度为6.25μM的VDC处理细胞时,抑制了超过50%的Aurora B活性。VDC通过抑制Aurora B激酶的活性能够在中期诱导染色体比对中的缺陷,是VDC作为抗肿瘤药的重要机制。
更新日期:2018-07-13
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