Neferine, a novel ROCK1-targeting inhibitor, blocks EMT process and induces apoptosis in non-small cell lung cancer.
Po HuPeng WanAnna XuBinghui YanChunmei LiuQixuan XuZhenhuan WeiJingyi XuSiqi LiuGuangming YangYang PanPublished in: Journal of cancer research and clinical oncology (2022)
The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of antitumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn.) also exerts antitumor effects on cancers. In this study, the effects and mechanisms of Nef on epithelial-to-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC) were evaluated. The results showed that Nef had the antitumor effects in vivo and in vitro. Nef significantly suppressed cell viability and induced apoptosis in NSCLC cells, with elevated reactive oxygen species and reduced BCL2/BAX ratio. Nef was also demonstrated to inhibit the invasion, metastasis and EMT process of NSCLC cells, and attenuate EMT-related changes of E-cadherin, N-cadherin and Vimentin at both transcriptional and translational levels. Moreover, we concluded that the inhibitory effects of Nef on EMT was achieved by targeting Rho-associated protein kinase 1, a protein mediating the process of EMT in various cancers. These results showed that Nef had a significant antitumor effect on NSCLC cells by inducing apoptosis and blocking EMT, providing the therapeutical prospect on NSCLC treatment.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- epithelial mesenchymal transition
- signaling pathway
- small cell lung cancer
- oxidative stress
- cell cycle arrest
- advanced non small cell lung cancer
- protein kinase
- cell death
- reactive oxygen species
- brain metastases
- gene expression
- cell migration
- binding protein
- transcription factor
- small molecule
- cell proliferation
- epidermal growth factor receptor
- smoking cessation