Investigating the anti-lung cancer properties of Zhuang medicine Cycas revoluta Thunb. leaves targeting ion channels and transporters through a comprehensive strategy.

Autor: De L; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Meishan Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: 857570432@qq.com., Xing N; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: xingnan@stu.cdutcm.edu.cn., Du Q; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: 448088718@qq.com., Guo S; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: 1057020534@qq.com., Wang S; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Meishan Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: winter9091@163.com.
Jazyk: angličtina
Zdroj: Computational biology and chemistry [Comput Biol Chem] 2024 Oct; Vol. 112, pp. 108156. Date of Electronic Publication: 2024 Jul 19.
DOI: 10.1016/j.compbiolchem.2024.108156
Abstrakt: Background: Cycas revoluta Thunb., known for its ornamental, economic, and medicinal value, has leaves often discarded as waste. However, in ethnic regions of China, the leaves (CRL) are used in folk medicine for anti-tumor properties, particularly for regulating pathways related to cancer. Recent studies on ion channels and transporters (ICTs) highlight their therapeutic potential against cancer, making it vital to identify CRL's active constituents targeting ICTs in lung cancer.
Purpose: This study aims to uncover bioactive substances in CRL and their mechanisms in regulating ICTs for lung cancer treatment using network pharmacology, bioinformatics, molecular docking, molecular dynamics (MD) simulations, in vitro cell assays and HPLC.
Methods: We analyzed 62 CRL compounds, predicted targets using PubChem and SwissTargetPrediction, identified lung cancer and ICT targets via GeneCards, and visualized overlaps with R software. Interaction networks were constructed using Cytoscape and STRING. Gene expression, GO, and KEGG analyses were performed using R software. TCGA data provided insights into differential, correlation, survival, and immune analyses. Key interactions were validated through molecular docking and MD simulations. Main biflavonoids were quantified using HPLC, and in vitro cell viability assays were conducted for key biflavonoids.
Results: Venn diagram analysis identified 52 intersecting targets and ten active CRL compounds. The PPI network highlighted seven key targets. GO and KEGG analysis showed CRL-targeted ICTs involved in synaptic transmission, GABAergic synapse, and proteoglycans in cancer. Differential expression and correlation analysis revealed significant differences in five core targets in lung cancer tissues. Survival analysis linked EGFR and GABRG2 with overall survival, and immune infiltration analysis associated the core targets with most immune cell types. Molecular docking indicated strong binding of CRL ingredients to core targets. HPLC revealed amentoflavone as the most abundant biflavonoid, followed by hinokiflavone, sciadopitysin, and podocarpusflavone A. MD simulations showed that podocarpusflavone A and amentoflavone had better binding stability with GABRG2, and the cell viability assay also proved that they had better anti-lung cancer potential.
Conclusions: This study identified potential active components, targets, and pathways of CRL-targeted ICTs for lung cancer treatment, suggesting CRL's utility in drug development and its potential beyond industrial waste.
Competing Interests: Declaration of Competing Interest The authors declare that there have no conflicts of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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