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Environ Toxicol Pharmacol. 2019 May 27;70:103200. doi: 10.1016/j.etap.2019.103200. [Epub ahead of print]

Bioinformatic and experimental data decipher the pharmacological targets and mechanisms of plumbagin against hepatocellular carcinoma.

Author information

1
Department of Hepatobiliary Surgery, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi, PR China.
2
Department of Pharmacy, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University, Guangxi, Nanning, PR China.
3
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, PR China.
4
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, PR China. Electronic address: lirong1278@163.com.

Abstract

OBJECTIVE:

Plumbagin exerts effective anti-hepatocellular carcinoma (HCC) benefits, however, the detailed mechanisms behind these effects are not yet completely elucidated. The pharmacological targets and molecular mechanisms of plumbagin against HCC were revealed through conducting network pharmacology approach before experimentative verification.

METHODS:

The web-accessible databases of herbal ingredients' targets (HIT), Swiss-Target-Prediction and Super-Pred were used to predict the therapeutic targets of plumbagin, followed by combined with pathogenic targets of HCC from oncogenomic database of hepatocellular carcinoma (OncoDB.HCC) and Liverome databases to obtain the predominant targets of plumbagin-treating HCC. The database for annotation, visualization and integrated discovery (DAVID) was applied to output the gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment by use of all predominant targets for computerized visualization. The validated data of human and cell culture were subjected to a group of medical imaging, biochemical tests and immunostaining, respectively.

RESULTS:

As revealed in bioinformatic data, 19 predominant targets of plumbagin-treating HCC were obtained, and 5 top targets of TP53, MAPK1, MAP2K1, RAF1 and CCND1 were the most important biomolecules in anti-HCC effects exerted by plumbagin. Other identifiable 102 GO items were showed, including 66 biological processes, and 12 cellular components, 24 molecular functions. And 67 KEGG pathways were mainly involved in neoplastic signaling. In human data, HCC sections showed increased expressions of hepatocellular TP53, MAPK1, accompanied with positive clinical imaging results for HCC. In plumbagin-treated HepG2 cells, reduced TP53, MAPK1 protein expressions were observed, accompanied with cell arrest and apoptosis.

CONCLUSION:

Collectively, the pharmacological targets and mechanisms of plumbagin-treating HCC were predicted and integrated through the method of network pharmacology, followed by some investigative validations. Interestingly, these 5 predominant biomolecules may be the potential targets for screening and treating HCC.

KEYWORDS:

Hepatocellular carcinoma; Molecular mechanisms; Network pharmacology; Plumbagin; Targets

PMID:
31158732
DOI:
10.1016/j.etap.2019.103200

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