包永明

个人信息Personal Information

教授

博士生导师

硕士生导师

性别:男

毕业院校:大连理工大学

学位:博士

所在单位:生物工程学院

学科:生物化工. 生物化学与分子生物学. 生物工程与技术

办公地点:大连理工大学生物工程楼323;盘锦校区D06 302室

联系方式:E-mail:biosci@dlut.edu.cn Tel:13332280036

电子邮箱:biosci@dlut.edu.cn

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Quercetin exerts synergetic anti-cancer activity with 10-hydroxy camptothecin

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论文类型:期刊论文

发表时间:2017-11-15

发表刊物:EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

收录刊物:Scopus、SCIE、PubMed

卷号:109

页面范围:223-232

ISSN号:0928-0987

关键字:Quercetin; 10-Hydroxy camptothecin; Cancer therapeutic; Topoisomerase I; Cell cycle; Apoptosis

摘要:Quercetin (Qu) is known as a dietary antioxidant with numerous bioactivities, but its function in anti-cancer has not been fully investigated. Here, we show that Qu at low doses (<= 10 mu M) significantly enhances the inhibition of 10-hydroxy camptothecin (HCPT) on the proliferation of MCF7, BGC823 and HepG2 cells. A plasmid DNA relaxation assay indicates that the inhibition of HCPT on the catalytic activity of topoisomerase I (Topo I) is increased by Qu at 10 mu M. Compared to the treatment by Qu or HCPT alone, phosphorylation at Ser(139) of gamma H2A. X in MCF7 cells starts to increase significantly (P < 0.05) at 6 h when treated by the combination of 10 mu M Qu and 0.62 mu M HCPT. Moreover, the combinational group successively arrests MCF7 cells at G1, S and G2/M phases from 12 h to 48 h via up-regulation of p21 and induces apoptosis at 24 h by triggering intrinsic cell death pathways. In addition, the inhibition effects of the combinational group on the proliferation of MCF7 cells are eliminated by pretreatment with 100 mu M Z-VAD-FMK (a caspase inhibitor). Finally, by using nude mice xenografting assay of MCF7 cells, we demonstrate that tumor inhibition rates of combinational group are significantly higher than single-drug group. In summary, the synergic anti-cancer mechanism of Qu and HCPT in MCF7 cells is through the combined inhibitory effects of Qu and HCPT on Topo I, which synergistically induce cell cycle arrest and apoptosis by triggering DNA damage.