PUBLICATION
In vitro and in vivo accumulation of the anticancer Ru complexes [RuII(cym)(HQ)Cl] and [RuII(cym)(PCA)Cl]Cl
- Authors
- Riisom, M., Morrow, S.J., Herbert, C.D., Tremlett, W.D.J., Astin, J.W., Jamieson, S.M.F., Hartinger, C.G.
- ID
- ZDB-PUB-231115-3
- Date
- 2023
- Source
- Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 28(8): 767-775 (Journal)
- Registered Authors
- Astin, Jonathan, Herbert, Caitlin
- Keywords
- Cellular accumulation, Hydroxyquinoline, LA-ICP-MS, Pyridinecarbothioamide, Ru anticancer complexes, Zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents*/chemistry
- Antineoplastic Agents*/pharmacology
- Cell Line, Tumor
- Cisplatin
- Coordination Complexes*/chemistry
- Coordination Complexes*/pharmacology
- Humans
- Ruthenium*/chemistry
- Zebrafish
- PubMed
- 37962611 Full text @ J. Biol. Inorg. Chem.
Citation
Riisom, M., Morrow, S.J., Herbert, C.D., Tremlett, W.D.J., Astin, J.W., Jamieson, S.M.F., Hartinger, C.G. (2023) In vitro and in vivo accumulation of the anticancer Ru complexes [RuII(cym)(HQ)Cl] and [RuII(cym)(PCA)Cl]Cl. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 28(8):767-775.
Abstract
The cellular accumulation and the underlying mechanisms for the two ruthenium-based anticancer complexes [RuII(cym)(HQ)Cl] 1 (cym = η6-p-cymene, HQ = 8-hydroxyquinoline) and [RuII(cym)(PCA)Cl]Cl 2 (PCA = N-fluorophenyl-2-pyridinecarbothioamide) were investigated in HCT116 human colorectal carcinoma cells. The results showed that the cellular accumulation of both complexes increased over time and with higher concentrations, and that 2 accumulates in greater quantities in cells than 1. Inhibition studies of selected cellular accumulation mechanisms indicated that both 1 and 2 may be transported into the cells by both passive diffusion and active transporters, similar to cisplatin. Efflux experiments indicated that 1 and 2 are subjected to efflux through a mechanism that does not involve p-glycoprotein, as addition of verapamil did not make any difference. Exploring the influence of the Cu transporter by addition of CuCl2 resulted in a higher accumulation of 1 and 2 whilst the amount of Pt detected was slightly reduced when cells were treated with cisplatin. Complexes 1 and 2 were further explored in zebrafish where accumulation and distribution were determined with ICP-MS and LA-ICP-MS. The results correlated with the in vitro observations and zebrafish treated with 2 showed higher Ru contents than those treated with 1. The distribution studies suggested that both complexes mainly accumulated in the intestines of the zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping