PUBLICATION
In Vitro and In Vivo Biological Activity of Ruthenium 1,10-Phenanthroline-5,6-dione Arene Complexes
- Authors
- Lenis-Rojas, O.A., Roma-Rodrigues, C., Carvalho, B., Cabezas-Sainz, P., Fernández Vila, S., Sánchez, L., Baptista, P.V., Fernandes, A.R., Royo, B.
- ID
- ZDB-PUB-221115-38
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(21): (Journal)
- Registered Authors
- Cabezas-Sainz, Pablo
- Keywords
- ROS, Ru-dione complexes, anticancer activity, autophagy, zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents*/pharmacology
- Antineoplastic Agents*/therapeutic use
- Cell Line, Tumor
- Cell Proliferation
- Coordination Complexes*/pharmacology
- Female
- Humans
- Ovarian Neoplasms*/drug therapy
- Ruthenium*/pharmacology
- Ruthenium*/therapeutic use
- Zebrafish
- PubMed
- 36362381 Full text @ Int. J. Mol. Sci.
Citation
Lenis-Rojas, O.A., Roma-Rodrigues, C., Carvalho, B., Cabezas-Sainz, P., Fernández Vila, S., Sánchez, L., Baptista, P.V., Fernandes, A.R., Royo, B. (2022) In Vitro and In Vivo Biological Activity of Ruthenium 1,10-Phenanthroline-5,6-dione Arene Complexes. International Journal of Molecular Sciences. 23(21):.
Abstract
Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η6-arene)Ru(L)Cl][X] X = CF3SO3 (JHOR10) and PF6 (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping