Activation of Nrf2 by Microcystin-LR Provides Advantages for Liver Cancer Cell Growth

被引：56
作者：
Gan, Nanqin [1 ]
Sun, Xiaoyun [1 ]
Song, Lirong [1 ]
机构：
[1] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
来源：
CHEMICAL RESEARCH IN TOXICOLOGY | 2010年 / 23卷 / 09期
关键词：
MITOCHONDRIAL PERMEABILITY TRANSITION; TRANSCRIPTION FACTOR NRF2; OXIDATIVE STRESS; LUNG-CANCER; NAD(P)H-QUINONE OXIDOREDUCTASE; INDUCED APOPTOSIS; RAT HEPATOCYTES; PROTECTION; KEAP1; STABILIZATION;
D O I：
10.1021/tx1001628
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Microcystin-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.
引用
收藏
页码：1477 / 1484
页数：8
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