Abstract
Fucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein–protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.
Highlights
Fucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties
Functional enrichment analyses of GO biological process on the genes of cluster 1 were performed by DAVID6.8, showing cell proliferation, apoptosis, cell cycle, angiogenesis, Non-small cell lung cancer (NSCLC) gene expression, invasion and migration, signal transduction, and NSCLC related signaling pathways (Fig. 3)
Through the NSCLC-related pathway map, we discover that GRB2 can be acted as the trigger or initiation signal of the Raf/MEK/ERK pathway by PI3K-Akt signaling pathway and ErbB signaling pathway, which may be crucial for fucosterol in the treatment of NSCLC
Summary
Fucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. The effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. Our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs. Abbreviations NSCLC Non-small cell lung cancer LUAD Lung adenocarcinoma GRB2 Growth factor receptor-binding protein 2 KEGG Kyoto encyclopedia of gene and genome GO Gene ontology PPI Protein-protein interaction TIMER Tumor immune estimation resource. Fucosterol belongs to algal phytosterol in ethanol extract of brown algae (a kind of macroalgae in the ocean), which has been proved to have multiple biological activities, including antioxidant[15,16,17], anti-inflammatory18–20, anticancer21, antimicrobial[22], anti-depression[23], etc. Previous researches have reported fucosterol on anti-cervical cancer[21], anti-leukemia[24], anti-colorectal cancer[25], etc., but there are few studies on the mechanism of fucosterol in treating NSCLC about its potential therapeutic targets and related pathways in detail
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
