Evaluation of the In Vitro and In Vivo Efficacy of Ruthenium Polypyridyl Compounds against Breast Cancer

Abstract

The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)–polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)–polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2 Ru1 and [{Ru(bipy)2}2(μ-C12H8N6-N,N)][CF3SO3]4 Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L−1. Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)–polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy.

A Review of the Role of the Zebrafish (Danio reiro) in Preclinical and Clinical Models of Biomarker Identification and Drug Targeting, and Developments in Personalized Medicine in Breast Cancer

“…The anti-cancer potential of [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2 Ru1 and [{Ru(bipy)2}2(μ-C12H8N6-N,N)][CF3SO3]4 Ru2 ruthenium complexes was studied in an MCF7 ZF xenograft model [ 75 ]. Both newly developed active compounds effectively prevented MCF7 proliferation and inhibited tumor growth compared to control in MCF7 BC cell ZF xenografts, with no significant signs of lethality observed.…”

“…Both newly developed active compounds effectively prevented MCF7 proliferation and inhibited tumor growth compared to control in MCF7 BC cell ZF xenografts, with no significant signs of lethality observed. Therefore, both compounds show potential for further in vivo mouse studies, as well as for their use as scaffolds for further chemical modifications to improve their drug-like properties ( Table 1 ) [ 75 ].…”

Fine-tuning the cytotoxicity of ruthenium(ii) arene compounds to enhance selectivity against breast cancers

“…26 Note that many other ruthenium complexes also display activity against breast cancers in vivo. [27][28][29] Since RAPTA compounds display promising activity in MCF-7 and MDA-MB-231 breast cancer cells but are not strongly cytotoxic, we hypothesized that more cytotoxic RAPTAlike complexes might offer enhanced activity against breast cancers while potentially retaining selectivity. Hence, we report a study assessing the in vitro effects of a series of rutheniumarene (RAPTA-type or RAPTA-like) compounds on MCF-7 and MDA-MB-231 breast cancer cell lines and non-tumorigenic L929 fibroblasts.…”

“…26 Note that many other ruthenium complexes also display activity against breast cancers in vivo. 27–29…”