Cellular and molecular response to ruthenium(II)-arene complex with substituted picolinato ligand in HeLa cells

Ruthenium(II)-arene complexes are promising drug candidates for therapy of solid tumors. We have previously shown that ruthenium(II)-arene complex [Ru(η6-p-cymene)(L7)Cl] (RuT7) exerts cytotoxic effects in a panel of cancer cell lines (J. Organomet. Chem. 2014, 749, 343–349). In this study we analyzed in vitro cellular response and performed whole-transcriptome microarray gene expression analysis in HeLa cells in order to understand the cellular and molecular mechanism of response to RuT7 complex. Results on biological action of ruthenium complex obtained on cellular level were reflected on molecular level as well. Analysis of functional categories and signaling and biochemical pathways that are associated with HeLa cells' response to ruthenium complex revealed that RuT7 complex leads HeLa cells through intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage made by action of reactive oxygen species and through direct DNA binding of RuT7. Performed molecular toxicity analysis has shown that RuT7 has fewer associated toxicity profiles than cisplatin. Altogether these results provide the basis for development of RuT7 in animal and pre-clinical studies as a potential drug candidate. We hybridized each condition (control, RuT7 and CDDP) at each time point (12 h and 24 h) in triplicate, for a total of 18 samples.