Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis
Abstract Non‐small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyropto...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12752 |
| _version_ | 1797633734742114304 |
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| author | Peng‐Cheng Zhong Zhi‐Wen Liu Qi‐Chang Xing Jia Chen Rui‐Pei Yang |
| author_facet | Peng‐Cheng Zhong Zhi‐Wen Liu Qi‐Chang Xing Jia Chen Rui‐Pei Yang |
| author_sort | Peng‐Cheng Zhong |
| collection | DOAJ |
| description | Abstract Non‐small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF‐β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus‐mediated gain‐of‐function studies of TGF‐β and MST1 were applied to validate the roles of TGF‐β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF‐β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF‐β in either in vitro or mouse‐transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF‐β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients. |
| first_indexed | 2024-03-11T11:58:01Z |
| format | Article |
| id | doaj.art-aba3f9192ac840a3be6f2675e349e78b |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-03-11T11:58:01Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-aba3f9192ac840a3be6f2675e349e78b2023-11-08T12:00:32ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-11-0139111106111810.1002/kjm2.12752Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosisPeng‐Cheng Zhong0Zhi‐Wen Liu1Qi‐Chang Xing2Jia Chen3Rui‐Pei Yang4Department of Integrated Traditional Chinese and Western Medicine Xiangtan Central Hospital Xiangtan ChinaResearch Institute for Future Food The Hong Kong Polytechnic University, Hong Kong Special Administrative Region Hong Kong ChinaDepartment of Pharmaceutical Xiangtan Central Hospital Xiangtan ChinaDepartment of Pharmaceutical Xiangtan Central Hospital Xiangtan ChinaLaboratory of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine Shenzhen ChinaAbstract Non‐small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF‐β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus‐mediated gain‐of‐function studies of TGF‐β and MST1 were applied to validate the roles of TGF‐β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF‐β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF‐β in either in vitro or mouse‐transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF‐β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.https://doi.org/10.1002/kjm2.12752MST1NeferineNSCLCPyroptosisTGF‐β |
| spellingShingle | Peng‐Cheng Zhong Zhi‐Wen Liu Qi‐Chang Xing Jia Chen Rui‐Pei Yang Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis Kaohsiung Journal of Medical Sciences MST1 Neferine NSCLC Pyroptosis TGF‐β |
| title | Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis |
| title_full | Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis |
| title_fullStr | Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis |
| title_full_unstemmed | Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis |
| title_short | Neferine inhibits the development of lung cancer cells by downregulating TGF‐β to regulate MST1/ROS‐induced pyroptosis |
| title_sort | neferine inhibits the development of lung cancer cells by downregulating tgf β to regulate mst1 ros induced pyroptosis |
| topic | MST1 Neferine NSCLC Pyroptosis TGF‐β |
| url | https://doi.org/10.1002/kjm2.12752 |
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