Ru(II)-Naphthoquinone complexes with high selectivity for triple-negative breast cancer

Autor(es)

Oliveira, Katia M. ^{[1, 2]} ; Peterson, Erica J. ^{[3, 4]} ; Carroccia, Murilo C. ^[5] ; Cominetti, Marcia R. ^[6] ; Deflon, Victor M. ^[5] ; Farrell, Nicholas P. ^{[3, 4]} ; Batista, Alzir A. ^[2] ; Correa, Rodrigo S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Ouro Preto, Dept Quim, ICEB, BR-35400000 Ouro Preto, MG - Brazil

^[2] Univ Fed Sao Carlos UFSCar, Dept Quim, Rodovia Washington Luis, KM 235 CP 676, BR-13561901 Sao Carlos, SP - Brazil

^[3] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 - USA

^[4] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23294 - USA

^[5] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

^[6] Univ Fed Sao Carlos, Dept Gerontol, Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DALTON TRANSACTIONS; v. 49, n. 45, p. 16193-16203, DEC 7 2020.
• Citações Web of Science: 5

Resumo

Six new ruthenium(ii) complexes with lapachol (Lap) and lawsone (Law) with the general formula {[}Ru(L)(P-P)(bipy)]PF6, where L = Lap or Law, P-P = 1,2 `-bis(diphenylphosphino)ethane (dppe), 1,4 `-bis(diphenylphosphino)butane (dppb), 1,1 `-bis(diphenylphosphino)ferrocene (dppf) and bipy = 2,2 `-bipyridine, were synthesized, fully characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis, IR spectroscopies and three of them by X-ray crystallography. All six complexes were active against breast (MCF-7 and MDA-MB-231) and prostate (DU-145) cancer cell lines with lower IC50 values than cisplatin. Complex {[}Ru(Lap)(dppe)(bipy)]PF6 (1a) showed significant selectivity for MDA-MB-231, a model of triple-negative breast cancer (TNBC), as compared to the ``normal-like{''} human breast epithelial cell line, MCF-10A. Complex (1a) inhibited TNBC colony formation and induced loss of cellular adhesion. Furthermore, the complex (1a) induced mitochondrial dysfunction and generation of ROS, as is involved in the apoptotic cell death pathway. Preferential cellular uptake of complex (1a) was observed in MDA-MB-231 cells compared to MCF-10A cells, consistent with the observed selectivity for tumorigenic vs. non-tumorigenic cells. Taken together, these results indicate that ruthenium complexes containing lapachol and lawsone as ligands are promising candidates as chemotherapeutic agents. (AU)

• Processo FAPESP: 14/04147-9 - Avaliação das propriedades anticâncer de complexos de rutênio(II) contendo os bioligantes lapachol e lausona
• Beneficiário: Katia Mara de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/18530-4 - A avaliação do mecanismo de ação de complexos de rutênio contendo produtos naturais bioativos
• Beneficiário: Katia Mara de Oliveira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 16/16312-0 - Citotoxidade e mecanismo de ação de complexos de rutênio contendo produtos naturais ou derivados
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular