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, [Cu(II)(5-Cl-pap)(OAc)(H(2)O)]·2H(2)O (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.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P R China.
Zhong-Ying
ZY
Ma
Xin
X
Qiao
Cheng-Zhi
CZ
Xie
Jia
J
Shao
Jing-Yuan
JY
Xu
Zhao-Yan
ZY
Qiang
Jian-Shi
JS
Lou
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012545:Schiff Bases; D003300:Copper; D053148:Caspase 3; D053453:Caspase 9