Baicalein, as a Prooxidant, Triggers Mitochondrial Apoptosis in MCF-7 Human Breast Cancer Cells Through Mobilization of Intracellular Copper and Reactive Oxygen Species Generation

Autor: Zheng-Hong Liu, Xiu-Quan Xu, Cong-Ying Yang, Lei Zhang, Cheng-Xi Yang
Rok vydání: 2019
Předmět:
Zdroj: OncoTargets and therapy
ISSN: 1178-6930
Popis: Zheng-Hong Liu,1 Cheng-Xi Yang,1 Lei Zhang,1 Cong-Ying Yang,1 Xiu-Quan Xu2 1Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222061, People’s Republic of China; 2School of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of ChinaCorrespondence: Cheng-Xi YangDepartment of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222061, People’s Republic of ChinaEmail fengw125@126.comXiu-Quan XuSchool of Pharmacy, Jiangsu University, 301, Xuefu Road, Zhenjiang 212013, People’s Republic of ChinaEmail xxq781026@ujs.edu.cnBackground: Baicalein, a natural flavonoid derived from traditional Chinese herb Scutellaria baicalensis Georg (known as Huang Qin in Chinese), has been reported to exhibit notable antitumor activity in various cancer cells, including breast cancer. However, the detailed mechanisms underlying its induced apoptosis as a prooxidant in breast cancer cells are still unknown.Materials and methods: In this study, we investigated the effect of endogenous copper on cytotoxic activity of baicalin against human breast cancer MCF-7 cells in vitro.Results: Baicalein could remarkably reduce the cell viability in both dose- and time-dependent manners in MCF-7 cells but with lower cytotoxic effects on normal breast epithelial cells, MCF-10A. Such cell death could be prevented by pretreatment with Cu (I)-specific chelator neocuproine (Neo) and reactive oxygen species (ROS) scavengers. Meanwhile, baicalein could induce MCF-7 cell morphological changes, promote apoptotic cell death and increase the apoptotic cell number. Moreover, DCHF-DA staining, flow cytometry and Western blotting analyses proved that baicalein triggered the mitochondrial-dependent apoptotic pathway, as indicated by enhancement the level of intracellular ROS, disruption of mitochondrial membrane potential (ΔΨm), downregulation of anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, release of cytochrome C and activation of caspase-9 and caspase-3 in MCF-7 cells. The pretreatment with Neo remarkably weakened these effects of baicalein. Furthermore, we confirmed that the prooxidant action of baicalein involved the direct production of hydroxyl radicals through redox recycling of copper ions.Conclusion: These findings suggested that baicalein, acting as a prooxidant, could trigger apoptosis in MCF-7 cells occurs via the ROS-mediated intrinsic mitochondria-dependent pathway.Keywords: baicalein, human breast cancer MCF-7 cells, apoptosis, mitochondria-dependent pathways, prooxidant  
Databáze: OpenAIRE
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