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题名: NF-kappa B plays a key role in microcystin-RR-induced HeLa cell proliferation and apoptosis
作者: Chen, Liang1, 2; Zhang, Xin1, 3; Chen, Jun1; Zhang, Xuezhen3; Fan, Huihui1, 3; Li, Shangchun1, 2; Xie, Ping1, 3
关键词: Microcystin-RR ; NF-kappa B ; Cell proliferation ; Apoptosis ; Hormesis ; HeLa cells
刊名: TOXICON
发表日期: 2014-09-01
DOI: 10.1016/j.toxicon.2014.06.002
卷: 87, 期:1, 页:120-130
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
英文摘要: Microcystins (MCs) are well-known cyanobacterial toxins produced in eutrophic waters and can act as potential carcinogens and have caused serious risk to human health. However, pleiotropic even paradoxical actions of cells exposure to MCs have been reported, and the mechanisms of MC-induced tumorigenesis and apoptosis are still unknown. In this study, we performed the first comprehensive in vitro investigation on carcinogenesis associated with nuclear factor kappa B (NF-kappa B) and its downstream genes in HeLa cells (Human cervix adenocarcinoma cell line from epithelial cells) exposure to MC-RR. HeLa cells were treated with 0, 20, 40, 60, and 80 mu g/mL MC-RR for 4, 8, 12, and 24 h. HeLa cells presented dualistic responses to different doses of MCs. CCK8 assay showed that MC-RR exposure evidently enhanced cell viability of HeLa cells at lower MCs doses. Cell cycle and apoptosis analysis revealed that lower MCs doses promoted G(1)/S transition and cell proliferation while higher doses of MCs induced apoptosis, with a dose-dependent manner. Electrophoretic mobility shift assay (EMSA) revealed that MC-RR could increase/decrease NF-kappa B activity at lower/higher MC-RR doses, respectively. Furthermore, the expression of NF-kappa B downstream target genes including c-FLIP, cyclinD1, c-myc, and c-IAP2 showed the same variation trend as NF-kappa B activity both at mRNA and protein levels, which were induced by lower doses of MC-RR and suppressed by higher doses. Our data verified for the first time that NF-kappa B pathway may mediate MC-induced cell proliferation and apoptosis and provided a better understanding of the molecular mechanism for potential carcinogenicity of MC-RR. (C) 2014 Elsevier Ltd. All rights reserved.
关键词[WOS]: ZEBRAFISH DANIO-RERIO ; PRIMARY LIVER-CANCER ; OXIDATIVE STRESS ; IN-VIVO ; TRANSCRIPTION FACTORS ; PROTEOMIC ANALYSIS ; GENE-EXPRESSION ; DRINKING-WATER ; LR EXPOSURE ; C-MYC
语种: 英语
WOS记录号: WOS:000339145900015
ISSN号: 0041-0101
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20311
Appears in Collections:淡水生态学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Huazhong Agr Univ, Coll Fisheries, Minist Agr, Key Lab Freshwater Anim Breeding, Wuhan 430070, Peoples R China
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