Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD
Xanthoangelol (XAG), a major chalcone presents in Angelica keiskei, has been employed in research to develop functional supplements or drugs due to its various pharmacological activities. Here, we investigated the underlying mechanism of XAG-induced cell death in hepatocellular carcinoma (HCC). We f...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464621002267 |
| _version_ | 1818733514461282304 |
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| author | Xuening Pang Xiang Gao Feng Liu Yuhuan Jiang Mingji Wang Qun Li Zichao Li |
| author_facet | Xuening Pang Xiang Gao Feng Liu Yuhuan Jiang Mingji Wang Qun Li Zichao Li |
| author_sort | Xuening Pang |
| collection | DOAJ |
| description | Xanthoangelol (XAG), a major chalcone presents in Angelica keiskei, has been employed in research to develop functional supplements or drugs due to its various pharmacological activities. Here, we investigated the underlying mechanism of XAG-induced cell death in hepatocellular carcinoma (HCC). We found that XAG inhibited the cell viability of either HepG2 or HuH7cells, and induced pyroptotic death in HuH7 cell with concomitant activation of NOD-like receptor family pyrin domain containing 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway. However, in GSDMD-low HepG2 cells, Caspase-1 expression modulated the underlying XAG-induced apoptosis pathway, thereby regulating cell death. VX-765, a special inhibitor of caspase-1, attenuated XAG-induced pyroptosis and apoptosis. Additionally, mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway were suppressed by XAG. These findings suggest that XAG is a promising therapeutic agent through induction of caspase-1 mediated pyroptosis and apoptosis depend on the expression of GSDMD in HCC cells. |
| first_indexed | 2024-12-17T23:50:41Z |
| format | Article |
| id | doaj.art-1d5f8e0f8d044aa98ddb097528db3be7 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-17T23:50:41Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-1d5f8e0f8d044aa98ddb097528db3be72022-12-21T21:28:12ZengElsevierJournal of Functional Foods1756-46462021-09-0184104577Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMDXuening Pang0Xiang Gao1Feng Liu2Yuhuan Jiang3Mingji Wang4Qun Li5Zichao Li6Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, ChinaInstitute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, ChinaNingbo City College of Vocational Technology, Department of Horticultural Technology, Ningbo 315199, China; Joint Institute of Angelica Keiskei Health Industry Technology, Qingdao University, Qingdao 266071, ChinaInstitute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, ChinaJoint Institute of Angelica Keiskei Health Industry Technology, Qingdao University, Qingdao 266071, ChinaJoint Institute of Angelica Keiskei Health Industry Technology, Qingdao University, Qingdao 266071, China; College of Chemistry and Chemical Engineering, Qingdao University, Qingdao 266071, ChinaInstitute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, China; Joint Institute of Angelica Keiskei Health Industry Technology, Qingdao University, Qingdao 266071, China; Corresponding author at: Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao 266071, China.Xanthoangelol (XAG), a major chalcone presents in Angelica keiskei, has been employed in research to develop functional supplements or drugs due to its various pharmacological activities. Here, we investigated the underlying mechanism of XAG-induced cell death in hepatocellular carcinoma (HCC). We found that XAG inhibited the cell viability of either HepG2 or HuH7cells, and induced pyroptotic death in HuH7 cell with concomitant activation of NOD-like receptor family pyrin domain containing 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway. However, in GSDMD-low HepG2 cells, Caspase-1 expression modulated the underlying XAG-induced apoptosis pathway, thereby regulating cell death. VX-765, a special inhibitor of caspase-1, attenuated XAG-induced pyroptosis and apoptosis. Additionally, mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway were suppressed by XAG. These findings suggest that XAG is a promising therapeutic agent through induction of caspase-1 mediated pyroptosis and apoptosis depend on the expression of GSDMD in HCC cells.http://www.sciencedirect.com/science/article/pii/S1756464621002267XanthoangelolAngelica keiskeiPyroptosisApoptosisHepatocellular carcinomaCaspase-1-dependent |
| spellingShingle | Xuening Pang Xiang Gao Feng Liu Yuhuan Jiang Mingji Wang Qun Li Zichao Li Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD Journal of Functional Foods Xanthoangelol Angelica keiskei Pyroptosis Apoptosis Hepatocellular carcinoma Caspase-1-dependent |
| title | Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD |
| title_full | Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD |
| title_fullStr | Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD |
| title_full_unstemmed | Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD |
| title_short | Xanthoangelol modulates Caspase-1-dependent pyroptotic death among hepatocellular carcinoma cells with high expression of GSDMD |
| title_sort | xanthoangelol modulates caspase 1 dependent pyroptotic death among hepatocellular carcinoma cells with high expression of gsdmd |
| topic | Xanthoangelol Angelica keiskei Pyroptosis Apoptosis Hepatocellular carcinoma Caspase-1-dependent |
| url | http://www.sciencedirect.com/science/article/pii/S1756464621002267 |
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