Skip to main content

ORIGINAL RESEARCH article

Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1471109

Mechanism of luteolin against non-small-cell lung cancer: A study based on network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments

Provisionally accepted
Jihang Zhang Jihang Zhang 1Changling Li Changling Li 2Wenyi Li Wenyi Li 1Zhenpeng Shi Zhenpeng Shi 1Zhenguo Liu Zhenguo Liu 1Zhou JunYu Zhou JunYu 1Jing Tang Jing Tang 1Zixuan Ren Zixuan Ren 1Yun Qiao Yun Qiao 2Deshan Liu Deshan Liu 2*
  • 1 Shandong University of Traditional Chinese Medicine, Jinan, China
  • 2 Qilu Hospital, Shandong University, Jinan, Shandong Province, China

The final, formatted version of the article will be published soon.

    Luteolin, a naturally occurring flavonoid compound, demonstrates promising anti-cancer properties. However, its mechanism against non-small-cell lung cancer (NSCLC) remains unknown. This study employed network pharmacology, molecular docking, molecular dynamics simulation (MDS), and in vitro experiments to investigate the potential mechanisms by which luteolin against NSCLC. Initially, the potential targets of luteolin and NSCLC-related targets were identified from public databases such as TCMSP, GeneCards, OMIM, DrugBank, and TTD. Subsequently, the protein-protein interaction (PPI) network screening and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The binding affinity and stability of luteolin with the core targets were assessed using molecular docking and MDS. Finally, the results were validated by in vitro experiments. A total of 56 luteolin targets and 2145 NSCLC-related targets were identified. Six core targets, TP53, EGFR, AKT1, TNF, JUN, and CASP3, were screened via the PPI network. The GO and KEGG analyses indicated that luteolin's activity against NSCLC potentially involves PI3K-Akt, NF-kappa B, and other signaling pathways. Molecular docking revealed that luteolin had high binding affinity with the core targets. MDS confirmed the stable interaction between luteolin and key proteins TP53 and AKT1. In vitro, luteolin significantly inhibited the proliferation and migration of A549 cells, while also inducing apoptosis. In addition, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax, which was consistent with the effect of LY294002. Collectively, luteolin had a good anti-NSCLC effect, and the apoptosis-inducing effect might be related to the Akt/MDM2/p53 signaling pathway.

    Keywords: ：Luteolin, Network Pharmacology, non-small-cell lung cancer, Akt/MDM2/p53 signaling pathway, in vitro experiments

    Received: 26 Jul 2024; Accepted: 21 Oct 2024.

    Copyright: © 2024 Zhang, Li, Li, Shi, Liu, JunYu, Tang, Ren, Qiao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Deshan Liu, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.