@Article{096504018X15462920753012,
AUTHOR = {Qing Wei,
 Rui Zhu,
 Junying Zhu, Rongping Zhao, Min Li},
TITLE = {E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis  and Inhibits Autophagy in HCC Cells},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {7},
PAGES = {827--834},
URL = {http://www.techscience.com/or/v27n7/48612},
ISSN = {1555-3906},
ABSTRACT = {Emerging evidence suggests that 17β-estradiol (E2) and estrogen receptor (ER) signaling are protective against 
hepatocellular carcinoma (HCC). In our previous study, we showed that E2 suppressed the carcinogenesis and 
progression of HCC by targeting NLRP3 inflammasome activation, whereas the molecular mechanism by which 
the NLRP3 inflammasome initiated cancer cell death was not elucidated. The present study aimed to investigate 
the effect of NLRP3 inflammasome activation on cell death pathways and autophagy of HCC cells. First, we 
observed an increasing mortality in E2-treated HCC cells, and then apoptotic and pyroptotic cell death were 
both detected. The mortality of HCC cells was largely reversed by the caspase 1 antagonist, YVAD-cmk, suggesting that E2-induced cell death was associated with caspase 1-dependent pyroptosis. Second, the key role 
of the NLRP3 inflammasome in autophagy of HCC cells was assessed by E2-induced activation of the NLRP3 
inflammasome, and we demonstrated that autophagy was inhibited by the NLRP3 inflammasome via the E2/
ERβ/AMPK/mTOR pathway. Last, the interaction of pyroptosis and autophagy was confirmed by flow cytometry methods. We observed that E2-induced pyroptosis was dramatically increased by 3-methyladenine (3-MA) 
treatment, which was abolished by YVAD-cmk treatment, suggesting that caspase 1-dependent pyroptosis was 
negatively regulated by autophagy. In conclusion, E2-induced activation of the NLRP3 inflammasome may 
serve as a suppressor in HCC progression, as it triggers pyroptotic cell death and inhibits protective autophagy.},
DOI = {10.3727/096504018X15462920753012}
}