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NF-kappa B plays a key role in microcystin-RR-induced HeLa cell proliferation and apoptosis
Chen, Liang1,2; Zhang, Xin1,3; Chen, Jun1; Zhang, Xuezhen3; Fan, Huihui1,3; Li, Shangchun1,2; Xie, Ping1,3
2014-09-01
Source PublicationTOXICON
ISSN0041-0101
Volume87Issue:1Pages:120-130
AbstractMicrocystins (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.
SubtypeArticle
KeywordMicrocystin-rr Nf-kappa b Cell Proliferation Apoptosis Hormesis Hela Cells
DOI10.1016/j.toxicon.2014.06.002
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS KeywordZEBRAFISH DANIO-RERIO ; PRIMARY LIVER-CANCER ; OXIDATIVE STRESS ; IN-VIVO ; TRANSCRIPTION FACTORS ; PROTEOMIC ANALYSIS ; GENE-EXPRESSION ; DRINKING-WATER ; LR EXPOSURE ; C-MYC
WOS IDWOS:000339145900015
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/20311
Collection淡水生态学研究中心
Affiliation1.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
Recommended Citation
GB/T 7714
Chen, Liang,Zhang, Xin,Chen, Jun,et al. NF-kappa B plays a key role in microcystin-RR-induced HeLa cell proliferation and apoptosis[J]. TOXICON,2014,87(1):120-130.
APA Chen, Liang.,Zhang, Xin.,Chen, Jun.,Zhang, Xuezhen.,Fan, Huihui.,...&Xie, Ping.(2014).NF-kappa B plays a key role in microcystin-RR-induced HeLa cell proliferation and apoptosis.TOXICON,87(1),120-130.
MLA Chen, Liang,et al."NF-kappa B plays a key role in microcystin-RR-induced HeLa cell proliferation and apoptosis".TOXICON 87.1(2014):120-130.
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