TY  - JOUR
AU  - Jovanović, Katarina K.
AU  - Tanić, Miljana
AU  - Ivanović, Ivanka
AU  - Gligorijević, Nevenka
AU  - Dojčinović, Biljana P.
AU  - Radulović, Siniša
PY  - 2016
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6318
AB  - Ruthenium(II)arene complexes are promising drug candidates for the therapy of solid tumors. Inprevious work, seven new compounds of the general formula [Ru(η6-p-cymene)(L1–7)Cl] were synthesized and characterized, of which the complex with L=isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by IC50 values determined after48 h of incubation (45.4±3.0 vs. 84.2±5.7 μM, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population.The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru / 10 6 cells after 6 h of incubation.To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygens pecies, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand
VL  - 163
SP  - 362
EP  - 373
DO  - 10.1016/j.jinorgbio.2016.04.011
ER  - 

@article{
author = "Jovanović, Katarina K. and Tanić, Miljana and Ivanović, Ivanka and Gligorijević, Nevenka and Dojčinović, Biljana P. and Radulović, Siniša",
year = "2016",
abstract = "Ruthenium(II)arene complexes are promising drug candidates for the therapy of solid tumors. Inprevious work, seven new compounds of the general formula [Ru(η6-p-cymene)(L1–7)Cl] were synthesized and characterized, of which the complex with L=isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by IC50 values determined after48 h of incubation (45.4±3.0 vs. 84.2±5.7 μM, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population.The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru / 10 6 cells after 6 h of incubation.To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygens pecies, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand",
volume = "163",
pages = "362-373",
doi = "10.1016/j.jinorgbio.2016.04.011"
}

Jovanović, K. K., Tanić, M., Ivanović, I., Gligorijević, N., Dojčinović, B. P.,& Radulović, S.. (2016). Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand. in Journal of Inorganic Biochemistry
Elsevier., 163, 362-373.
https://doi.org/10.1016/j.jinorgbio.2016.04.011

Jovanović KK, Tanić M, Ivanović I, Gligorijević N, Dojčinović BP, Radulović S. Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand. in Journal of Inorganic Biochemistry. 2016;163:362-373.
doi:10.1016/j.jinorgbio.2016.04.011 .

Jovanović, Katarina K., Tanić, Miljana, Ivanović, Ivanka, Gligorijević, Nevenka, Dojčinović, Biljana P., Radulović, Siniša, "Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand" in Journal of Inorganic Biochemistry, 163 (2016):362-373,
https://doi.org/10.1016/j.jinorgbio.2016.04.011 . .