| Status | 已發表Published |
| Investigation on anti-cancer effects and mechanisms of a norditerpenoid from seeds of Podocarpus nagi | |
Zhang, LL ; Feng, ZL; Guo, J; Zheng, MZ; Chen, X. P.; Wang, Y. T.; Li, A; Li, H; Lin, L.  ; Lu, J.
| |
| 2018-06-01 | |
| Source Publication | N/A
 |
| Abstract | Non-small cell lung cancer (NSCLC) is one of most common forms and leading causes of cancer-related mortality worldwide. Discovery of new effective drugs still remains imperative for the improvement of the survival rate. In our previous study, nine new norditerpenoids and dinorditerpenoids, along with several known analogues, were isolated from the seeds of Podocarpus nagi and identified as cytotoxic agents and autophagy inducers. Among them, a norditerpenoid PNE6C exhibited remarkable anticancer potential against NSCLC. PNE6C inhibited proliferation of epidermal growth factor receptor (EGFR) wild-type A549 and EGFR T790M mutant NCI-H1975 cells via induction of G2 phase cell cycle arrest. PNE6C treatment decreased the protein level of cyclin B1 as well as its nuclear accumulation, which might result from the translation inhibitory effect of PNE6C. Besides, the effect of PNE6C on migration and invasion of NSCLC cells was also investigated. PNE6C could obviously inhibit TGF-β/Smad signaling pathway in A549 cells, thereafter inhibited TGF-β1 induced epithelial-mesenchymal transition and migration and invasion. RNA-seq analysis was performed to identify the underlying molecular mechanisms contributing to the effect of PNE6C. In particular, analysis of the RNA-seq results using the CMap dataset indicated PNE6C to be a novel protein synthesis inhibitor, which has been further confirmed by the Click-IT assay. In vivo, PNE6C treatment suppressed tumor growth in A549 xenograft bearing mice, while didn’t affect body weight or induce liver, spleen and kidney damage. Taken together, PNE6C inhibited proliferation, migration and invasion of NSCLC cells, and it possessed anti-cancer potential as a single agent against NSCLC. |
| Keyword | Norditerpenoid Podocarpus nagi Non-Small Cell Lung Cancer G2 Phase Cell Cycle Arrest Epithelial-Mesenchymal Transition Protein Synthesis Inhibitor |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 43849 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Lin, L.; Lu, J. |
| Recommended Citation GB/T 7714 | Zhang, LL,Feng, ZL,Guo, J,et al. Investigation on anti-cancer effects and mechanisms of a norditerpenoid from seeds of Podocarpus nagi[C], 2018. |
| APA | Zhang, LL., Feng, ZL., Guo, J., Zheng, MZ., Chen, X. P.., Wang, Y. T.., Li, A., Li, H., Lin, L.., & Lu, J. (2018). Investigation on anti-cancer effects and mechanisms of a norditerpenoid from seeds of Podocarpus nagi. N/A. |
| Files in This Item: | There are no files associated with this item. | |||||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment