Alpinumisoflavone suppresses hepatocellular carcinoma cell growth and metastasis via NLRP3 inflammasome-mediated pyropto
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ARTICLE
Alpinumisoflavone suppresses hepatocellular carcinoma cell growth and metastasis via NLRP3 inflammasome‑mediated pyroptosis Yan Zhang1 · Hong Yang1 · Meifeng Sun1 · Tingting He1 · Yufang Liu1 · Xiuwei Yang1 · Xiaoli Shi1 · Xiaoxiao Liu1 Received: 14 August 2019 / Revised: 15 December 2019 / Accepted: 13 February 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
Abstract Aim This research aims to explore the effect of alpinumisoflavone (AIF) as an anti-cancer drug for the treatment of patients with hepatocellular carcinoma (HCC). Methods Cell counting kit-8 (CCK-8) and colony formation assay were used to evaluate the viability of the cells and their clonogenic ability. Cellular migration and their invasion capabilities were detected using the wound-healing and transwell assay, respectively. The release of lactate dehydrogenase (LDH) was detected using the LDH kit. The expression levels of genes in the cells and tumor tissues were examined by qRT-PCR, western blotting, and immunohistochemical techniques. The cells transfected with mRFP-GFP-LC3 adenoviruses were stained to determine their autophagy status. MCC950 (NLRP3 inflammasome inhibitor) and NLRP3 shRNA were used to block NLRP3-mediated pyroptosis. Chloroquine and Atg 5 siRNA were used to inhibit the autophagy of the cells. Results AIF suppressed cell proliferation, migration, and invasion capacity of SMMC 7721 and Huh7 cells. The incorporation of AIF induced the formation of NLRP3 inflammasome assembly, pyroptosis, and autophagy of the cells. However, the anti-proliferative and anti-metastatic effects of AIF on the HCC cells were attenuated by NLRP3 inhibitor and knockdown. Furthermore, Atg 5 knockdown inhibited autophagy and enhanced the rate of AIF-induced pyroptosis of the cells. AIF also suppressed tumor growth and increased the levels of pyroptosis-related genes in tumor tissues, which were consistent with in vitro observations. Conclusion AIF inhibited HCC cell growth and metastasis by inducing NLRP3 inflammasome-mediated pyroptosis. Furthermore, AIF-induced autophagy augmented pyroptosis in HCC. Keywords Alpinumisoflavone · Hepatocellular carcinoma · Pyroptosis · NLRP3 · Autophagy
Introduction Liver cancer is the second most common cause of cancerrelated deaths after lung cancer. According to the latest estimates, 841,080 new cases of liver cancer (4.7% of total cases) and 781,631 deaths due to liver cancer were reported in 2018 (8.2% of total cancer deaths) [1]. Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43440-020-00064-8) contains supplementary material, which is available to authorized users. * Xiaoxiao Liu [email protected] 1
The Affiliated Hospital of Qingdao University, Jiangsu Road 16, Qingdao 266003, China
Typically, molecular-targeted drugs and immunotherapy are used to treat patients having hepatitis B and hepatitis C virus, which cause HCC in humans. However, such patients at an
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