| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1317796 | Journal of Inorganic Biochemistry | 2012 | 9 Pages |
In our previous study, ruthenium(II)-p-cymene complexes of general formula [(η6-p-cymene)Ru(L)Cl2], L: 3-acetylpyridine (1), 2-amino-5-chloropyridine (2); and [(η6-p-cymene)Ru(HL)Cl], HL: 2,3-pyridinedicarboxylic acid (3), 2,4-pyridinedicarboxylic acid (4), revealed low antiproliferative activity, except complex [(η6-p-cymene)RuCl(picolinic acid)]·H2O (5) which exhibited IC50 around 80 μM. In this study we further investigated in vitro potential of antimetastatic action of ruthenium complexes on HeLa and two endothelial cell lines. Comparison of structure and activity of five complexes indicated heterogenic mode of activity, with regard to the potential of antimetastatic and antiproliferative effect. Replacement of substituted pyridine ligand with picolinic acid (complex 5) around Ru(II) center contributed to complex cytotoxicity and ruthenium DNA binding affinity. Analysis of ruthenium(II) accumulation in DNA and protein fractions of HeLa cells, using ICP-OES revealed significantly higher content of complex 5 in DNA fraction in comparison to the other tested compounds. It also altered cell cycle progression, affected expression of DNA repair enzymes ERCC1 and MSH2, and showed enhanced activity in combination with 3-aminobenzamide.Regardless of their effect on cell growth, Ru(II) complexes exerted antimetastatic effect on several tumor cell lines in vitro, achieved mostly by the effect on cell adhesion, migration and angiogenesis, while picolinate ruthenium(II)–arene additionally exerted inhibitory effect on extracellular matrix degradation.
Graphical abstractComparison of in vitro antimetastatic and cytotoxic activity of several ruthenium(II)-p-cymene complexes reveled picolinate ruthenium(II)–arene complex as the most promising one, with highest DNA binding affinity, and highest inhibitory effect on metalloproteinase activity and angiogenesis.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Picolinate ruthenium(II)– arene exhibited antiproliferative and DNA binding property. ► It also showed in vitro antimetastatic properties. ► Influence of complex on DNA repair enzymes ERCC1, MSH2 and PARP was investigated.
