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

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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.
Funding Information
  • VLC-BIOCLINIC Program of the University of Valencia (02-RUN-AT-MARTINEZ-RIBAS-2017-A, PI-2021-007-DIRUGEN, POSTD20028OLTR, CPII14-00013, CB16/12/00481-CB16/12/00473)
  • FCAECC (02-RUN-AT-MARTINEZ-RIBAS-2017-A, PI-2021-007-DIRUGEN, POSTD20028OLTR, CPII14-00013, CB16/12/00481-CB16/12/00473)
  • Carlos III Health Institute (02-RUN-AT-MARTINEZ-RIBAS-2017-A, PI-2021-007-DIRUGEN, POSTD20028OLTR, CPII14-00013, CB16/12/00481-CB16/12/00473)
  • Centro de Investigación Biomédica en Red de Cáncer (02-RUN-AT-MARTINEZ-RIBAS-2017-A, PI-2021-007-DIRUGEN, POSTD20028OLTR, CPII14-00013, CB16/12/00481-CB16/12/00473)

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