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RUNAT-BI:一种作为针对高侵袭性癌细胞系的选择性抗肿瘤候选药物的钌(III)配合物。

RUNAT-BI: A Ruthenium(III) Complex as a Selective Anti-Tumor Drug Candidate against Highly Aggressive Cancer Cell Lines.

作者信息

Albanell-Fernández Marta, Oltra Sara S, Orts-Arroyo Marta, Ibarrola-Villava Maider, Carrasco Fany, Jiménez-Martí Elena, Cervantes Andrés, Castro Isabel, Martínez-Lillo José, Ribas Gloria

机构信息

INCLIVA Biomedical Research Institute, Hospital Clínico Universitario Valencia, University of Valencia, 46010 Valencia, Spain.

Instituto de Ciencia Molecular (ICMol)/Departament de Química Inorgànica, University of Valencia, 46980 Valencia, Spain.

出版信息

Cancers (Basel). 2022 Dec 22;15(1):69. doi: 10.3390/cancers15010069.

Abstract

Ruthenium compounds have demonstrated promising activity in different cancer types, overcoming several limitations of platinum-based drugs, yet their global structure-activity is still under debate. We analyzed the activity of Runat-BI, a racemic Ru(III) compound, and of one of its isomers in eight tumor cell lines of breast, colon and gastric cancer as well as in a non-tumoral control. Runat-BI was prepared with 2,2'-biimidazole and dissolved in polyethylene glycol. We performed assays of time- and dose-dependent viability, migration, proliferation, and expression of pro- and antiapoptotic genes. Moreover, we studied the growth rate and cell doubling time to correlate it with the apoptotic effect of Runat-BI. As a racemic mixture, Runat-BI caused a significant reduction in the viability and migration of three cancer cell lines from colon, gastric and breast cancer, all of which displayed fast proliferation rates. This compound also demonstrated selectivity between tumor and non-tumor lines and increased proapoptotic gene expression. However, the isolated isomer did not show any effect. Racemic Runat-BI is a potential drug candidate for treatment of highly aggressive tumors. Further studies should be addressed at evaluating the role of the other isomer, for a more precise understanding of its antitumoral potential and mechanism of action.

摘要

钌化合物在不同类型癌症中已显示出有前景的活性,克服了铂类药物的若干局限性,但其整体构效关系仍存在争议。我们分析了外消旋Ru(III)化合物Runat-BI及其一种异构体在八种乳腺癌、结肠癌和胃癌肿瘤细胞系以及一种非肿瘤对照中的活性。Runat-BI由2,2'-联咪唑制备并溶解于聚乙二醇中。我们进行了时间和剂量依赖性活力、迁移、增殖以及促凋亡和抗凋亡基因表达的测定。此外,我们研究了生长速率和细胞倍增时间以将其与Runat-BI的凋亡效应相关联。作为外消旋混合物,Runat-BI导致来自结肠癌、胃癌和乳腺癌的三种癌细胞系的活力和迁移显著降低,所有这些细胞系均显示出快速增殖率。该化合物还表现出肿瘤细胞系与非肿瘤细胞系之间的选择性,并增加了促凋亡基因的表达。然而,分离出的异构体未显示出任何作用。外消旋Runat-BI是治疗高侵袭性肿瘤的潜在候选药物。应进一步开展研究以评估另一种异构体的作用,以便更精确地了解其抗肿瘤潜力和作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79cb/9817854/6ae3acbd30cb/cancers-15-00069-g001.jpg

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