Ruthenium (II) complex cis-[Ru^II(?²-O₂CC₇H₇O₂)(dppm)₂]PF₆-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity

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Costa, Monica Soares ; Goncalves, Yasmim Garcia ; Borges, Bruna Cristina ; Barbosa Silva, Marcelo Jose ; Amstalden, Martin Kraehenbuehl ; Costa, Tassia Rafaella ; Greggi Antunes, Lusania Maria ; Rodrigues, Renata Santos ; Rodrigues, Veridiana de Melo ; Franca, Eduardo de Faria ; Pereira Zoia, Mariana Alves ; de Araujo, Thaise Goncalves ; Goulart, Luiz Ricardo ; Von Poelhsitz, Gustavo ; Geraldo Yoneyama, Kelly Aparecida

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1, p. 21-pg., 2020-09-21.

Abstract

Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[Ru-II(?(2)-O2CC7H7O2)(dppm)(2)]PF6 against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells. In addition, this complex at a concentration of 3.8 mu M was able to expressively increase the generation of reactive oxygen species (ROS) in tumor cells, causing an oxidative stress that may culminate in: (1) reduction in cellular proliferation; (2) changes in cell morphology and organization patterns of the actin cytoskeleton; (3) cell arrest in the G2/M phase of the cell cycle; (4) apoptosis; (5) changes in the mitochondrial membrane potential and (6) initial DNA damage. Furthermore, we demonstrated that the induction of programmed cell death can occur by the intrinsic apoptotic pathway through the activation of caspases. It is also worth highlighting that hmxbato exhibited predominant actions on A549 tumor cells in comparison to BEAS-2B normal bronchial epithelium cells, which makes this complex an interesting candidate for the design of new drugs against lung cancer. (AU)

• FAPESP's process: 14/24170-5 - DNA replication dynamics in Trypanosoma cruzi: licensing and replication rate characterization
• Grantee: Marcelo Santos da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral