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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1407525
This article is part of the Research Topic Systems Pharmacology in the Spotlight: Trending Technologies in Network Biology and Drug Discovery View all 9 articles
Mechanisms of action of Sappan Lignum for prostate cancer treatment: network pharmacology, molecular docking and experimental validation
Provisionally accepted- Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
Background: Prostate cancer (PCa) is the most common non-cutaneous malignancy in men globally. Sappan lignum, which exists in the heartwood of Caesalpinia sappan L., has antitumor effects; however, its exact mechanism of action remains unclear. This study elucidated the underlying mechanisms of Sappan lignum in PCa through network pharmacology approaches and molecular docking techniques. Moreover, the therapeutic effects of Sappan lignum on PCa were verified through in vitro experiments. Methods: The constituent ingredients of Sappan lignum were retrieved from the HERB database. Active plant-derived compounds of Sappan lignum were screened based on gastrointestinal absorption and gastric drug properties. Disease targets for PCa were screened using unpaired and paired case datasets from the Gene Expression Omnibus. Intersection targets were used for gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Core targets were identified through topological analysis parameters and their clinical relevance was validated through The Cancer Genome Atlas database. The affinity between the phytochemicals of Sappan lignum and core proteins was verified using the molecular docking technique. Validation experiments confirmed the significant potential of Sappan lignum in treating PCa. Results: Twenty-one plant-derived compounds of Sappan lignum and 821 differentially expressed genes associated with PCa were collected. Among 32 intersection targets, 8 were screened according to topological parameters. KEGG analysis indicated that the antitumor effects of Sappan lignum on PCa were primarily associated with the p53 pathway. The molecular docking technique demonstrated a strong affinity between 3-deoxysappanchalcone (3-DSC) and core proteins, particularly cyclin B1 (CCNB1). CCNB1 expression correlated with clinicopathological features in patients with PCa. Experimental results revealed that 3-DSC exhibited anti-proliferative, anti-migratory, and proapoptotic effects on 22RV1 and DU145 cells while also causing G2/M phase cell cycle arrest, potentially through modulating the p53/p21/CDC2/CCNB1 pathway.This research highlights the promising therapeutic potential of Sappan lignum in treating PCa, with a particular focus on targeting the p53 pathway.
Keywords: prostate cancer, Sappan Lignum, Network Pharmacology, molecular docking, P53 signaling pathway, experimental validation in vitro
Received: 26 Mar 2024; Accepted: 27 Aug 2024.
Copyright: © 2024 Li, Jiang, Zhang, Sun, Zhang, Xu, Huang and Wan. 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:
JInchang Huang, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
Yuxiang Wan, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
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