Activities of a novel Schiff Base copper(II) complex on growth inhibition and apoptosis induction toward MCF-7 human breast cancer cells via mitochondrial pathway

In this study, we investigated the newly synthesized Schiff base copper(II) complex, [CuII(5-Cl-pap)(OAc)(H2O)]·2H2O (1) (5-Cl-pap = N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine), inducing growth inhibition and apoptosis in human breast cancer cell line MCF-7 and its potential antitumor mechanism. The results of cytotoxicity research, fluorescence microscopic observation and flow cytometric analysis revealed that complex 1 could significantly suppress MCF-7 cell viability and induce apoptosis. Comet assay indicated that severe DNA fragmentation in MCF-7 cells was induced after treatment with complex 1. Flow cytometric analysis showed that the antitumor effect of complex 1 on MCF-7 cells was associated with the cell cycle arrest. In addition, atomic absorption analyses displayed that complex 1 caused a rapid increase of intracellular copper uptake in MCF-7 cells in a time-dependent manner. The present work suggested that the antitumor mechanism of complex 1 on MCF-7 cells might be via the mitochondrial pathway, based on the up-regulated expression of Bax and activation of caspase-9 and caspase-3.

Schiff base copper(II) complex induced growth inhibition and apoptosis toward MCF-7 cancer cells which identified as mitochondria-targeting pathway.Figure optionsDownload as PowerPoint slideHighlights
► Schiff base Cu(II) complex induced growth inhibition and apoptosis toward MCF-7 cancer cells.
► Cytotoxicity, fluorescence microscopic and flow cytometric analysis were employed.
► The complex was identified as mitochondria-targeting inducer based on the up-regulated expression of Bax and activation of caspase-9 and caspase-3.