Open Access
ARTICLE
E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells
Qing Wei1,
Rui Zhu1,
Junying Zhu, Rongping Zhao, Min Li
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China
Oncology Research 2019, 27(7), 827-834. https://doi.org/10.3727/096504018X15462920753012
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.
Keywords
Cite This Article
Wei, Q., Zhu,
. R., Zhu,
. J., Zhao, R., Li, M. (2019). E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells.
Oncology Research, 27(7), 827–834. https://doi.org/10.3727/096504018X15462920753012