Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

Cytisine is a natural product isolated from plants and is a member of the quinolizidine alkaloid family. This study aims to investigate the effect of cytisine in human lung cancer. Cell viability was determined using the CCK-8 assay, and the results showed that cytisine inhibited the growth of lung...

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Main Authors: Wan-Ting Xu, Tian-Zhu Li, Shu-Mei Li, Cheng Wang, Hao Wang, Ying-Hua Luo, Xian-Ji Piao, Jia-Ru Wang, Yu Zhang, Tong Zhang, Hui Xue, Long-Kui Cao, Cheng-Hao Jin
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Artificial Cells, Nanomedicine, and Biotechnology
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Online Access:https://www.tandfonline.com/doi/10.1080/21691401.2019.1699813
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author Wan-Ting Xu
Tian-Zhu Li
Shu-Mei Li
Cheng Wang
Hao Wang
Ying-Hua Luo
Xian-Ji Piao
Jia-Ru Wang
Yu Zhang
Tong Zhang
Hui Xue
Long-Kui Cao
Cheng-Hao Jin
author_facet Wan-Ting Xu
Tian-Zhu Li
Shu-Mei Li
Cheng Wang
Hao Wang
Ying-Hua Luo
Xian-Ji Piao
Jia-Ru Wang
Yu Zhang
Tong Zhang
Hui Xue
Long-Kui Cao
Cheng-Hao Jin
author_sort Wan-Ting Xu
collection DOAJ
description Cytisine is a natural product isolated from plants and is a member of the quinolizidine alkaloid family. This study aims to investigate the effect of cytisine in human lung cancer. Cell viability was determined using the CCK-8 assay, and the results showed that cytisine inhibited the growth of lung cancer cell lines. The apoptotic effects were evaluated using flow cytometry, and the results showed that cytisine induced mitochondrial-dependent apoptosis through loss of the mitochondrial membrane potential; increased expression of BAD, cleaved caspase-3, and cleaved-PARP; and decreased expression levels of Bcl-2, pro-caspase-3, and pro-PARP. In addition, cytisine caused G2/M phase cell cycle arrest that was associated with inhibiting the AKT signalling pathway. During apoptosis, cytisine increased the phosphorylation levels of JNK, p38, and I-κB, and decreased the phosphorylation levels of ERK, STAT3, and NF-κB. Furthermore, cytisine treatment led to the generation of ROS, and the NAC attenuated cytisine-induced apoptosis. In vivo, cytisine administration significantly inhibited the lung cancer cell xenograft tumorigenesis. In conclusion, cytisine plays a critical role in suppressing the carcinogenesis of lung cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, suggesting that it may be a promising candidate for the treatment of human lung cancer.
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series Artificial Cells, Nanomedicine, and Biotechnology
spelling doaj-art-759171be62ca4e29b0fec74ce6fe6f5e2025-08-20T03:41:47ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2020-01-01481849510.1080/21691401.2019.1699813Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathwaysWan-Ting Xu0Tian-Zhu Li1Shu-Mei Li2Cheng Wang3Hao Wang4Ying-Hua Luo5Xian-Ji Piao6Jia-Ru Wang7Yu Zhang8Tong Zhang9Hui Xue10Long-Kui Cao11Cheng-Hao Jin12Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaMolecular Medicine Research Center, School of Basic Medical Science, Chifeng University, Chifeng, ChinaHemodialysis Center, Daqing Oilfield General Hospital, Daqing, ChinaPharmacy Department, Daqing Oilfield General Hospital, Daqing, ChinaDepartment of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Grass Science, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Gynaecology and Obstetrics, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, ChinaDepartment of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Food Science and Engineering, College of Food Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaDepartment of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaCytisine is a natural product isolated from plants and is a member of the quinolizidine alkaloid family. This study aims to investigate the effect of cytisine in human lung cancer. Cell viability was determined using the CCK-8 assay, and the results showed that cytisine inhibited the growth of lung cancer cell lines. The apoptotic effects were evaluated using flow cytometry, and the results showed that cytisine induced mitochondrial-dependent apoptosis through loss of the mitochondrial membrane potential; increased expression of BAD, cleaved caspase-3, and cleaved-PARP; and decreased expression levels of Bcl-2, pro-caspase-3, and pro-PARP. In addition, cytisine caused G2/M phase cell cycle arrest that was associated with inhibiting the AKT signalling pathway. During apoptosis, cytisine increased the phosphorylation levels of JNK, p38, and I-κB, and decreased the phosphorylation levels of ERK, STAT3, and NF-κB. Furthermore, cytisine treatment led to the generation of ROS, and the NAC attenuated cytisine-induced apoptosis. In vivo, cytisine administration significantly inhibited the lung cancer cell xenograft tumorigenesis. In conclusion, cytisine plays a critical role in suppressing the carcinogenesis of lung cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, suggesting that it may be a promising candidate for the treatment of human lung cancer.https://www.tandfonline.com/doi/10.1080/21691401.2019.1699813Cytisinehuman lung cancer cellapoptosiscell cycle arrestreactive oxygen species
spellingShingle Wan-Ting Xu
Tian-Zhu Li
Shu-Mei Li
Cheng Wang
Hao Wang
Ying-Hua Luo
Xian-Ji Piao
Jia-Ru Wang
Yu Zhang
Tong Zhang
Hui Xue
Long-Kui Cao
Cheng-Hao Jin
Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways
Artificial Cells, Nanomedicine, and Biotechnology
Cytisine
human lung cancer cell
apoptosis
cell cycle arrest
reactive oxygen species
title Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways
title_full Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways
title_fullStr Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways
title_full_unstemmed Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways
title_short Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways
title_sort cytisine exerts anti tumour effects on lung cancer cells by modulating reactive oxygen species mediated signalling pathways
topic Cytisine
human lung cancer cell
apoptosis
cell cycle arrest
reactive oxygen species
url https://www.tandfonline.com/doi/10.1080/21691401.2019.1699813
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