Abstract
Abstractβ-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that β-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that β-elemene decreased the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human forkhead box class O (FOXO)3a; the latter two were abrogated in cells with overexpressed Stat3. Notably, miRNA155-5p mimics reduced FOXO3a luciferase reporter activity in the 3-UTR region and protein expression, whereas overexpressed FOXO3a countered the reduction of the miRNA155-5p levels by β-elemene. Moreover, β-elemene increased the mRNA and protein expression levels as well as promoter activity of insulin-like growth factor-binding protein 1 (IGFBP1); this finding was not observed in cells with a silenced FOXO3a gene and miRNA155-5p mimics. Finally, silencing of IGFBP1 blocked β-elemene-inhibited cell growth. Similar findings were observed in vivo. In summary, our results indicate that β-elemene increases IGFBP1 gene expression via inactivation of Stat3 followed by a reciprocal interaction between miRNA155-5p and FOXO3a. This effect leads to inhibition of human lung cancer cell growth. These findings reveal a novel molecular mechanism underlying the inhibitory effects of β-elemene on lung cancer cells.
Publisher
Springer Science and Business Media LLC
Subject
Clinical Biochemistry,Molecular Biology,Molecular Medicine,Biochemistry
Reference58 articles.
1. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer Statistics, 2017. Ca. Cancer J. Clin. 67, 7–30 (2017).
2. Chang, G. C. et al. Activity of gefitinib in advanced non-small-cell lung cancer with very poor performance status. Invest. New Drugs 23, 73–77 (2005).
3. Zhu, T. et al. Reversion of malignant phenotypes of human glioblastoma cells by beta-elemene through beta-catenin-mediated regulation of stemness-, differentiation- and epithelial-to-mesenchymal transition-related molecules. J. Transl. Med. 13, 356 (2015).
4. Liu, M. et al. beta-Elemene attenuates atherosclerosis in apolipoprotein E-deficient mice via restoring NO levels and alleviating oxidative stress. Biomed. Pharmacother. 95, 1789–1798 (2017).
5. Wang, Z., Li, Y., Zhou, F., Piao, Z. & Hao, J. beta-elemene enhances anticancer bone neoplasms efficacy of paclitaxel through regulation of GPR124 in bone neoplasms cells. Oncol. Lett. 16, 2143–2150 (2018).
Cited by
24 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献