IMR Press / FBL / Volume 27 / Issue 1 / DOI: 10.31083/j.fbl2701025
Open Access Original Research
Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments
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1 Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, China
2 Department of Traditional Chinese Medicine, Fujian Medical University Union Hospital, 350000 Fuzhou, Fujian, China
3 Fuqing Li Hualing TCM Clinic, 350000 Fuzhou, Fujian, China
4 Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, China
5 Department of neurology, Fujian Provincial Hospital, 350000 Fuzhou, Fujian, China
6 Department of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, China
*Correspondence: (Yongxiang Yi); (Junwei Li)
These authors contributed equally.
Academic Editor: Josef Jampilek
Front. Biosci. (Landmark Ed) 2022, 27(1), 25;
Submitted: 25 October 2021 | Revised: 6 December 2021 | Accepted: 22 December 2021 | Published: 17 January 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Hepatocellular carcinoma (HCC) is a common clinical malignant disease and the second leading cause of cancer-related death worldwide. Dendrobium is a commonly applied nourishing drug in traditional Chinese medicine. Gigantol is a phenolic compound extracted from Dendrobium. The compound has attracted attention for its anticancer effects. However, the mechanism of gigantol in HCC has not been extensively explored. Methods: Potential targets of gigantol were predicted by SwissTargetPrediction. HCC-related genes were obtained from the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), Therapeutic Target Database (TTD) and DrugBank databases. The “gigantol-target-disease” network was constructed using Cytoscape software. Protein interaction network analysis was performed using STRING software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were executed utilizing the R package to explore the possible regulatory mechanisms of gigantol in HCC. To authenticate the role of gigantol in HCC, Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) assay, wound healing assay, Matrigel invasion assay and Western blot were performed. Results: Three core genes were screened from 32 closely linked genes. Pathway analysis yielded many signaling pathways associated with cancer. The CCK-8 assay and EdU assay indicated that gigantol suppressed the growth of HCC cells. The wound healing assay and Matrigel invasion assay showed the inhibition of migration and metastasis of HCC cells by gigantol. We verified from molecular docking and protein level that gigantol can exert regulatory effects through three targets, ESR1, XIAP and HSP90AA1. Furthermore, Western blot results tentatively revealed that gigantol may inhibit HCC progression through the HSP90/Akt/CDK1 pathway. Conclusions: Our results confirms anti-HCC proliferation activity of gigantol through PI3K pathway described in existing literature by different experimental approaches. Furthermore, it has discovered other proteins regulated by the drug that was not previously reported in the literature.These findings provide potential molecular and cellular evidence that gigantol may be a promising antitumor agent.

Hepatocellular carcinoma
Network-based pharmacological
Molecular docking
Anti-HCC effect
Fig. 1.
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