Copper(II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action

Autor(es)

Tamayo, Lenka V. ^[1] ; Gouvea, Ligiane R. ^[1] ; Sousa, Anna C. ^[1] ; Albuquerque, Ronniel M. ^[1] ; Teixeira, Sarah Fernandes ^[2] ; de Azevedo, Ricardo Alexandre ^[2] ; Louro, Sonia R. W. ^[3] ; Ferreira, Adilson Kleber ^{[2, 4]} ; Beraldo, Heloisa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Dept Quim, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 Sao Paulo, SP - Brazil

^[3] Pontificia Univ Catolica Rio De Janeiro, Dept Fis, BR-22653900 Rio De Janeiro, RJ - Brazil

^[4] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Hanzepl 1, NL-9713 Groningen - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: BIOMETALS; v. 29, n. 1, p. 39-52, FEB 2016.
• Citações Web of Science: 13

Resumo

Copper(II) complexes {[}Cu(H (2) O) (2) (L1)(phen)](ClO (4) ) (1) and {[}Cu(H (2) O)(L2)(phen)](ClO (4) ) (2) (HL1 = naringenin; HL2 = hesperetin) were obtained, in which an anionic flavonoid ligand is attached to the metal center along with 1,10-phenanthroline (phen) as co-ligand. Complexes (1) and (2) were assayed for their cytotoxic activity against A549 lung carcinoma and against normal lung fibroblasts (LL-24) and human umbilical vein endothelial cells (HUVEC). We found IC50 = 16.42 A mu M (1) and IC50 = 5.82 A mu M (2) against A549 tumor cells. Complexes (1) and (2) exhibited slight specificity, being more cytotoxic against malignant than against non-malignant cells. 1 and 2 induced apoptosis on A549 cells in a mitochondria-independent pathway, and showed antioxidant activity. The antioxidant effect of the complexes could possibly improve their apoptotic action, most likely by a PI3K-independent reduction of autophagy. Complexes (1) and (2) interact in vitro with calf thymus DNA by an intercalative binding mode. EPR data indicated that 1 and 2 interact with human serum albumin (HSA) forming mixed ligand species. (AU)

• Processo FAPESP: 13/07273-2 - Planejamento racional e desenvolvimento de novos protótipos derivados de fosfolipídios antitumorais como inibidores potenciais da enzima CTP: fosfoetanolamina citidililtransferase e agentes antitumorais em carcinoma de pulmão de não pequenas células
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/54599-5 - Células dendríticas: elementos integrados do sistema imune - enfoque aplicado
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Temático