RUNAT-BI: A Ruthenium(III) Complex as a Selective Anti-Tumor Drug Candidate against Highly Aggressive Cancer Cell Lines

SIMPLE SUMMARY: To overcome some limitations of platinum-based chemotherapy agents, new active metallodrugs based on other transition metals are being researched. Runat-BI is a ruthenium-based compound which was synthesized and characterized at the University of Valencia. We investigated the in vitro effect of this compound on eight cell lines of different cancer types. Runat-BI reduced tumor growth and migration significantly in three cancer cell lines, showing selectivity for tumoral cells and little effect on non-tumoral ones. Its mechanism of action is still unknown but seems related to DNA synthesis as the cells with higher growth rates are the most affected by this chemotherapy agent. However, additional mechanism(s) likely play a role in its selectivity for several cancer cell lines. Moreover, Runat-BI slightly increases expression of the proapoptotic genes BAX and CASPASE-3. All these findings support its study as a potential anticancer therapy. ABSTRACT: Ruthenium compounds have demonstrated promising activity in different cancer types, overcoming several limitations of platinum-based drugs, yet their global structure–activity is still under debate. We analyzed the activity of Runat-BI, a racemic Ru(III) compound, and of one of its isomers in eight tumor cell lines of breast, colon and gastric cancer as well as in a non-tumoral control. Runat-BI was prepared with 2,2’-biimidazole and dissolved in polyethylene glycol. We performed assays of time- and dose-dependent viability, migration, proliferation, and expression of pro- and antiapoptotic genes. Moreover, we studied the growth rate and cell doubling time to correlate it with the apoptotic effect of Runat-BI. As a racemic mixture, Runat-BI caused a significant reduction in the viability and migration of three cancer cell lines from colon, gastric and breast cancer, all of which displayed fast proliferation rates. This compound also demonstrated selectivity between tumor and non-tumor lines and increased proapoptotic gene expression. However, the isolated isomer did not show any effect. Racemic Runat-BI is a potential drug candidate for treatment of highly aggressive tumors. Further studies should be addressed at evaluating the role of the other isomer, for a more precise understanding of its antitumoral potential and mechanism of action.