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Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth
Gan, Nanqin; Sun, Xiaoyun; Song, Lirong; Song, LR, CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
2010
Source PublicationCHEMICAL RESEARCH IN TOXICOLOGY
Volume23Issue:9Pages:1477-1484
AbstractMicrocystin-LR (MC-LR) is a potent heptapeptide hepatotoxin at high doses, but its underlying mechanism of promoting liver cell proliferation at low doses is unclear. The transcription factor nuclear factor erythroid 2-related factor 2 (Nr12) is key in mediating the protective antioxidant response against various environmental toxicants, but emerging data suggest that constitutive activation of Nrf2 contributes to a malignant phenotype. The purpose of this study was to characterize the interactions and effects of NrI2 activation on cell proliferation induced by MC-LR treatment. Treatment of HepG2 and Flep3B cells with MC-LR resulted in significant increases in Nrf2-ARE binding activities in the nuclear fractions and upregulation of its downstream genes HO-1 and NQO1. A possible mechanism may be that MC-LR binds to the cytosolic regulator protein Keap1 to liberate Nrf2. Nrf2 knockdown inhibited MC-LR-induced cell proliferation and cell cycle progression. Together, these results indicate that MC-LR-induced upregulation of Nrf2 in cancer cells promotes liver cancer cell growth and suggest a positive role of Nrf2 in tumorigenesis.
KeywordMitochondrial Permeability Transition Transcription Factor Nrf2 Oxidative Stress Lung-cancer Nad(p)H-quinone Oxidoreductase Induced Apoptosis Rat Hepatocytes Protection Keap1 Stabilization
Department[Gan, Nanqin; Sun, Xiaoyun; Song, Lirong] CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
Subject AreaChemistry ; Medicinal ; Multidisciplinary ; Chemistry ; Toxicology
Indexed BySCI
WOS IDWOS:000281840600006
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/13773
Collection藻类生物学及应用研究中心_期刊论文
Corresponding AuthorSong, LR, CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
Recommended Citation
GB/T 7714
Gan, Nanqin,Sun, Xiaoyun,Song, Lirong,et al. Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2010,23(9):1477-1484.
APA Gan, Nanqin,Sun, Xiaoyun,Song, Lirong,&Song, LR, CAS, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China.(2010).Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth.CHEMICAL RESEARCH IN TOXICOLOGY,23(9),1477-1484.
MLA Gan, Nanqin,et al."Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth".CHEMICAL RESEARCH IN TOXICOLOGY 23.9(2010):1477-1484.
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