Selective Ru(II)/lawsone complexes inhibiting tumor cell growth by apoptosis

Author(s)

Oliveira, Katia M. ^[1] ; Liany, Luna-Dulcey ^[2] ; Correa, Rodrigo S. ^[3] ; Deflon, Victor M. ^[4] ; Cominetti, Marcia R. ^[2] ; Batista, Alzir A. ^[1]

Affiliation

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

^[2] Univ Fed Sao Carlos, Dept Gerontol, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Fed Ouro Preto, Dept Quim, BR-35400000 Ouro Preto, MG - Brazil

^[4] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 176, p. 66-76, NOV 2017.
• Web of Science Citations: 18

Abstract

New Ru(II) complexes with lawsone (law) characterized as trans-{[}Ru(law)(PPh3)(2)(N-N)]PF6, where PPh3 means triphenylphosphine and N-N is 2,2'-bipyridine (1), 4,4'-dimethyl-2,2'-bipyridine (2), 4,4'-dimethoxy-2,2'-bipyridine (3), 1,10-phenanthroline (4) or 4,7-diphenyl-1,10-phenanthroline (5), induce apoptosis in tumor cells. Cytotoxicity of the complexes against the tumor cell lines DU-145 (prostate cancer cells), MCF-7 (breast cancer cells), A549 (lung cancer cells) and lung non-tumor cell line MRC-5 demonstrated promising IC50 values, lower than those found for the cisplatin, a drug used as a reference. Due to the high cytotoxic activity and selectivity against A549 cells line, complex (5) was selected for detailed assays. The complex (5) inhibits cells migration in concentrations in a nanomolar range, inducing tumor cell death by apoptosis, as confirmed by flow cytometry experiments. Furthermore, the antiproliferative activity of complex (5) on A549 tumor cells is attributed to a cell cycle arrest at the Sub G1 phase, followed by a decrease in the number of cells at the S phase. In addition, the interaction of the complexes (1-5) with CT-DNA was evaluated by circular dichroism, in which no changes in the secondary structure of DNA were observed, suggesting a weak interaction of the complexes with the biomolecule. On the other hand, complexes (1-5) showed a higher interaction with human serum albumin (HSA) by non-covalent van der Waals forces and hydrogen bonding, resulting in static quenching. (AU)

• FAPESP's process: 14/04147-9 - Evaluation of anticancer properties of ruthenium(II)complexes containing lapachol and lawsone bioligands
• Grantee: Katia Mara de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate