Ruthenium(II)-mercapto complexes induce cell damage via apoptosis pathway on ovarian cancer cells

Author(s)

Palmeira-Mello, Marcos, V ; Teixeira, Tamara ; de Melo, Matheus Reis Santos ; Nicolella, Heloiza Diniz ; Dutra, Jocely L. ; Cominetti, Marcia R. ; Rocha, Fillipe Vieira ; Tavares, Denise Crispim ; Batista, Alzir A.

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 265, p. 10-pg., 2025-01-04.

Abstract

Ovarian cancer represents a leading cause of cancer-related deaths in women worldwide. Chemotherapeutic agents are usually employed to treat the patients, and Ruthenium(II)-based compounds have been investigated as possible substitutes for platinum drugs. In this work, we studied three different Ru(II)-phosphine-mercapto complexes (1-3) as potential cytotoxic agents against A2780 and A2780-cisR ovarian cancer cells. A time- dependent cytotoxicity was observed for 2 , which also exhibited better selectivity than cisplatin control. A similar cytotoxic behavior was observed on 3D tumor spheroids. Although no changes were observed in cell cycle distribution, compound 2 affected the mitochondrial membrane potential on A2780 cells, and caused cell death via apoptotic pathway, which was confirmed by flow cytometry assay. Western blotting experiments revealed that 2 affected the expression of p53, PCNA, gamma H2AX and cleaved caspase-3, making it a promising anticancer agent for ovarian cancer. (AU)

• FAPESP's process: 22/02876-0 - Evaluation of the biological profile of coordination complexes: an approach in 2D and 3D cell models
• Grantee: Fillipe Vieira Rocha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/01787-0 - In vitro and in vivo study of Ru(II)/phosphine complexes with anticancer activities
• Grantee: Marcos Vinícius Palmeira de Mello
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/02475-8 - Phosphine Ru(II) complexes with naphthoquinones and derivatives: potential anticancer, estudies in vitro and in vivo
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants