In:
Metallomics, Oxford University Press (OUP), Vol. 13, No. 4 ( 2021-04-24)
Abstract:
A novel optically pure dinuclear copper(II) complex of a rosin derivative dehydroabietic acid (DHA, HL) was synthesized and fully characterized. The in vitro antitumor activities of the copper(II) complex Cu2(µ2-O)(L)4(DMF)2 (1) were explored and compared with those of a trinuclear iron(III) complex [Fe3(µ3-O)(L)6(CH3OH)2(CH3O)]·H2O (2). 1 was more cytotoxic than 2, and the in vitro cytotoxicity of 1 was comparable to that of cisplatin and oxaliplatin. The metal coordination improved the cytotoxicity of DHA. 1 could arrest cycle in G1 phase and induce apoptosis in MCF-7 cell. 1 increased reactive oxygen species level, GSSG/GSH ratio, and Ca2+ production, and caused the loss of mitochondrial membrane potential (Δψm) in MCF-7 cells. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-9/caspase-3 activation, and the release of Cyt c demonstrate that 1 triggered mitochondria-mediated intrinsic apoptosis in MCF-7 cells. Caspase-8/caspase-4 activation and up-regulated Fas expression indicate that death receptor-mediated extrinsic apoptosis was included. Comet assay and up-regulated γ-H2AX and p53 expressions confirmed that 1 caused DNA damage in MCF-7 cells. Moreover, 1 led to enhancement of the biomarker of lipid peroxidation and the indicator of protein carbonylation in MCF-7 cells. All the results suggest that 1 could kill MCF-7 cells by generating oxidative stress, impairing DNA, promoting lipid peroxidation and protein carbonylation, and inducing apoptosis and autophagy. Furthermore, 1 also displayed antimetastatic activities with inhibition of cell invasion and migration, together with antiangiogenesis properties. On the whole, copper complex based on rosin derivatives is worth developing as metal-based antitumor drugs.
Type of Medium:
Online Resource
ISSN:
1756-591X
DOI:
10.1093/mtomcs/mfab014
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2021
detail.hit.zdb_id:
2474317-3
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