Centipeda minima active components and mechanisms in lung cancer

Abstract Background Traditional Chinese medicine (TCM) has been extensively used for neoplasm treatment and has provided many promising therapeutic candidates. We previously found that Centipeda minima (C. minima), a Chinese medicinal herb, showed anti-cancer effects in lung cancer. However, the act...

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Main Authors: Cuiyun Gao, Huafeng Pan, Fengjun Ma, Ze Zhang, Zedan Zhao, Jialing Song, Wei Li, Xiangzhen Fan
Format: Article
Language:English
Published: BMC 2023-03-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-023-03915-y
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author Cuiyun Gao
Huafeng Pan
Fengjun Ma
Ze Zhang
Zedan Zhao
Jialing Song
Wei Li
Xiangzhen Fan
author_facet Cuiyun Gao
Huafeng Pan
Fengjun Ma
Ze Zhang
Zedan Zhao
Jialing Song
Wei Li
Xiangzhen Fan
author_sort Cuiyun Gao
collection DOAJ
description Abstract Background Traditional Chinese medicine (TCM) has been extensively used for neoplasm treatment and has provided many promising therapeutic candidates. We previously found that Centipeda minima (C. minima), a Chinese medicinal herb, showed anti-cancer effects in lung cancer. However, the active components and underlying mechanisms remain unclear. In this study, we used network pharmacology to evaluate C. minima active compounds and molecular mechanisms in lung cancer. Methods We screened the TCMSP database for bioactive compounds and their corresponding potential targets. Lung cancer-associated targets were collected from Genecards, OMIM, and Drugbank databases. We then established a drug-ingredients-gene symbols-disease (D-I-G-D) network and a protein–protein interaction (PPI) network using Cytoscape software, and we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using R software. To verify the network pharmacology results, we then performed survival analysis, molecular docking analysis, as well as in vitro and in vivo experiments. Results We identified a total of 21 C. minima bioactive compounds and 179 corresponding targets. We screened 804 targets related to lung cancer, 60 of which overlapped with C. minima. The top three candidate ingredients identified by D-I-G-D network analysis were quercetin, nobiletin, and beta-sitosterol. PPI network and core target analyses suggested that TP53, AKT1, and MYC are potential therapeutic targets. Moreover, molecular docking analysis confirmed that quercetin, nobiletin, and beta-sitosterol, combined well with TP53, AKT1, and MYC respectively. In vitro experiments verified that quercetin induced non-small cell lung cancer (NSCLC) cell death in a dose-dependent manner. GO and KEGG analyses found 1771 enriched GO terms and 144 enriched KEGG pathways, including a variety of cancer related pathways, the IL-17 signaling pathway, the platinum drug resistance pathway, and apoptosis pathways. Our in vivo experimental results confirmed that a C. minima ethanol extract (ECM) enhanced cisplatin (CDDP) induced cell apoptosis in NSCLC xenografts. Conclusions This study revealed the key C. minima active ingredients and molecular mechanisms in the treatment of lung cancer, providing a molecular basis for further C. minima therapeutic investigation.
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spelling doaj.art-4e4aeee1e495413b8d5e704520c5708f2023-03-26T11:06:39ZengBMCBMC Complementary Medicine and Therapies2662-76712023-03-0123112010.1186/s12906-023-03915-yCentipeda minima active components and mechanisms in lung cancerCuiyun Gao0Huafeng Pan1Fengjun Ma2Ze Zhang3Zedan Zhao4Jialing Song5Wei Li6Xiangzhen Fan7Department of Rehabilitation Medicine, Binzhou Medical University HospitalScience and Technology Innovation Center, Guangzhou University of Chinese MedicineShandong University of Traditional Chinese MedicineSchool of Rehabilitation Medicine, Binzhou Medical UniversitySchool of Rehabilitation Medicine, Binzhou Medical UniversitySchool of Rehabilitation Medicine, Binzhou Medical UniversityDepartment of Rehabilitation Medicine, Binzhou Medical University HospitalDepartment of Rehabilitation Medicine, Binzhou Medical University HospitalAbstract Background Traditional Chinese medicine (TCM) has been extensively used for neoplasm treatment and has provided many promising therapeutic candidates. We previously found that Centipeda minima (C. minima), a Chinese medicinal herb, showed anti-cancer effects in lung cancer. However, the active components and underlying mechanisms remain unclear. In this study, we used network pharmacology to evaluate C. minima active compounds and molecular mechanisms in lung cancer. Methods We screened the TCMSP database for bioactive compounds and their corresponding potential targets. Lung cancer-associated targets were collected from Genecards, OMIM, and Drugbank databases. We then established a drug-ingredients-gene symbols-disease (D-I-G-D) network and a protein–protein interaction (PPI) network using Cytoscape software, and we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using R software. To verify the network pharmacology results, we then performed survival analysis, molecular docking analysis, as well as in vitro and in vivo experiments. Results We identified a total of 21 C. minima bioactive compounds and 179 corresponding targets. We screened 804 targets related to lung cancer, 60 of which overlapped with C. minima. The top three candidate ingredients identified by D-I-G-D network analysis were quercetin, nobiletin, and beta-sitosterol. PPI network and core target analyses suggested that TP53, AKT1, and MYC are potential therapeutic targets. Moreover, molecular docking analysis confirmed that quercetin, nobiletin, and beta-sitosterol, combined well with TP53, AKT1, and MYC respectively. In vitro experiments verified that quercetin induced non-small cell lung cancer (NSCLC) cell death in a dose-dependent manner. GO and KEGG analyses found 1771 enriched GO terms and 144 enriched KEGG pathways, including a variety of cancer related pathways, the IL-17 signaling pathway, the platinum drug resistance pathway, and apoptosis pathways. Our in vivo experimental results confirmed that a C. minima ethanol extract (ECM) enhanced cisplatin (CDDP) induced cell apoptosis in NSCLC xenografts. Conclusions This study revealed the key C. minima active ingredients and molecular mechanisms in the treatment of lung cancer, providing a molecular basis for further C. minima therapeutic investigation.https://doi.org/10.1186/s12906-023-03915-yCentipeda minimaLung cancerNetwork pharmacologyMolecular dockingExperimental validationMolecular mechanism
spellingShingle Cuiyun Gao
Huafeng Pan
Fengjun Ma
Ze Zhang
Zedan Zhao
Jialing Song
Wei Li
Xiangzhen Fan
Centipeda minima active components and mechanisms in lung cancer
BMC Complementary Medicine and Therapies
Centipeda minima
Lung cancer
Network pharmacology
Molecular docking
Experimental validation
Molecular mechanism
title Centipeda minima active components and mechanisms in lung cancer
title_full Centipeda minima active components and mechanisms in lung cancer
title_fullStr Centipeda minima active components and mechanisms in lung cancer
title_full_unstemmed Centipeda minima active components and mechanisms in lung cancer
title_short Centipeda minima active components and mechanisms in lung cancer
title_sort centipeda minima active components and mechanisms in lung cancer
topic Centipeda minima
Lung cancer
Network pharmacology
Molecular docking
Experimental validation
Molecular mechanism
url https://doi.org/10.1186/s12906-023-03915-y
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AT zezhang centipedaminimaactivecomponentsandmechanismsinlungcancer
AT zedanzhao centipedaminimaactivecomponentsandmechanismsinlungcancer
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