Heterobimetallic Ru(ii)/Fe(ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targets

Author(s):Show less -

Mundim Guedes, Adriana Pereira ^[1] ; Mello-Andrade, Francyelli ^{[2, 3]} ; Pires, Wanessa Carvalho ^[2] ; Montes de Sousa, Maria Alice ^[4] ; Faustino da Silva, Paula Francinete ^[2] ; de Camargo, Mariana S. ^[1] ; Gemeiner, Hendryk ^[5] ; Amauri, Menegario A. ^[5] ; Cardoso, Clever Gomes ^[6] ; de Melo Reis, Paulo Roberto ^[4] ; Silveira-Lacerda, Elisangela de Paula ^[2] ; Batista, Alzir A. ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Chem, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Goias, Inst Biol Sci, Dept Genet, BR-74690900 Goiania, Go - Brazil

^[3] Fed Inst Educ Sci & Technol Goias, Dept Chem, BR-74055110 Goiania, Go - Brazil

^[4] Pontifical Catholic Univ Goias, Lab Expt & Biotechnol Res, Masters Program Environm Sci & Hlth, Sch Med Sci, Pharmaceut & Biomed Lab, BR-74605010 Goiania, Go - Brazil

^[5] Sao Paulo State Univ, Ctr Environm Studies, BR-13506900 Rio Claro, SP - Brazil

^[6] Univ Fed Goias, Inst Biol Sci, Dept Morphol, BR-74690900 Goiania, Go - Brazil

• Document type: Journal article
• Source: METALLOMICS; v. 12, n. 4, p. 547-561, APR 1 2020.
• Web of Science Citations: 0

Abstract

Antimetastatic activity, high selectivity and cytotoxicity for human tumor cell lines make ruthenium(ii) complexes attractive for the development of new chemotherapeutic agents for cancer treatment. In this study, cytotoxic activities and the possible mechanism of cell death induced by three ruthenium complexes were evaluated, {[}Ru(MIm)(bipy)(dppf)]PF6(1), {[}RuCl(Im)(bipy)(dppf)]PF6(2) and {[}Ru(tzdt)(bipy)(dppf)]PF6(3). The results showed high cytotoxicity and selectivity indexes for the human triple-negative breast tumor cell line (MDA-MB-231) with IC(50)value and selectivity index for complex1(IC50= 0.33 +/- 0.03 mu M, SI = 4.48), complex2(IC50= 0.80 +/- 0.06 mu M, SI = 2.31) and complex3(IC50= 0.48 +/- 0.02 mu M, SI = 3.87). The mechanism of cell death induced in MDA-MB-231 cells, after treatment with complexes1-3, indicated apoptosis of the cells as a consequence of the increase in the percentage of cells in the Sub-G1 phase in the cell cycle analysis, characteristic morphological changes and the presence of apoptotic cells labeled with Annexin-V. Multiple targets of action were identified for complexes1and3with an induction of DNA damage in cells treated with complexes1and3, mitochondrial depolarization with a reduction in mitochondrial membrane potential, an increase in reactive oxygen species levels and increased expression levels of caspase 3 and p53. In addition, antimetastatic activities for complexes1and3were observed by inhibition of cell migration by the wound healing assay and Boyden chamber assay, as well as inhibition of angiogenesis caused by MDA-MB-231 tumor cells in the CAM model. (AU)

• FAPESP's process: 16/16312-0 - CYTOTOXICITY AND MECHANISM OF ACTION OF RUTHENIUM COMPLEXES CONTAINING NATURAL PRODUCTS OR DERIVATIVES
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants