期刊
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
卷 48, 期 1, 页码 84-95出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/21691401.2019.1699813
关键词
Cytisine; human lung cancer cell; apoptosis; cell cycle arrest; reactive oxygen species
资金
- Postdoctoral Scientific Research Foundation of Heilongjiang Province of China [LBH-Q13132]
- National key research and development plan [2017YFD0401203]
- Heilongjiang Farms & Land Reclamation Administration Support Project for Key Scientific Research [HKKYZD190705]
- Heilongjiang Bayi Agricultural University Support Programme for 'San Zong' [TDJH201905]
- Scientific Research Innovation Programme for College Graduates of Heilongjiang Bayi Agricultural University [YJSCX2019-Y69]
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-kappa B, and decreased the phosphorylation levels of ERK, STAT3, and NF-kappa B. 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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