Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells

Author(s)

Popolin, Cecilia P. ; Reis, Joao P. B. ; Becceneri, Amanda B. ; Graminha, Angelica E. ; Almeida, Marcio A. P. ; Correa, Rodrigo S. ; Colina-Vegas, Legna A. ; Ellena, Javier ; Batista, Alzir A. ; Cominetti, Marcia R.

• Document type: Journal article
• Source: PLoS One; v. 12, n. 9 SEP 12 2017.
• Web of Science Citations: 13

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1) {[}Ru(SO4) (dppb)(bipy)], (2) {[}Ru(CO3)(dppb)(bipy)], (3) {[}Ru(C2O4)(dppb)(bipy)] and (4) {[}Ru(CH3CO2) (dppb)(bipy)]PF6 {[}where dppb = 1,4-bis(diphenylphosphino) butane and bipy = 2,2'-bipyridine], on proliferation of TNBC (MDA-MB-231), estrogen-dependent breast tumor cells (MCF-7) and a non-tumor breast cell line (MCF-10A). Complex (4) was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4) was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4) was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4) should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment. (AU)

• FAPESP's process: 13/00798-2 - The extracellular matrix in aging, exercise and in the tumor microenvironment
• Grantee: Heloisa Sobreiro Selistre de Araújo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/24940-8 - EFFECTIVENESS OF STRUCTURAL CHANGES IN [10]-GINGEROL MOLECULE IN COMBINATION WITH THE CHEMOTHERAPEUTIC DOXORUBICIN FOR THE TREATMENT OF BREAST CANCER: IN VITRO AND IN VIVO STUDIES. ABSTRACT
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Regular Research Grants