Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments
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...
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| Format: | Article |
| Language: | English |
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IMR Press
2022-01-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/27/1/10.31083/j.fbl2701025 |
| _version_ | 1819025910128443392 |
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| author | Shujie Li Hualing Li Dandan Yin Xiaojing Xue Xiaoling Chen Xiaoyue Li Junwei Li Yongxiang Yi |
| author_facet | Shujie Li Hualing Li Dandan Yin Xiaojing Xue Xiaoling Chen Xiaoyue Li Junwei Li Yongxiang Yi |
| author_sort | Shujie Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T05:18:11Z |
| format | Article |
| id | doaj.art-44c7950ba34344738d9d99148bde537f |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-12-21T05:18:11Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-44c7950ba34344738d9d99148bde537f2022-12-21T19:14:52ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-01-0127102510.31083/j.fbl2701025S2768-6701(22)00363-XEffect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experimentsShujie Li0Hualing Li1Dandan Yin2Xiaojing Xue3Xiaoling Chen4Xiaoyue Li5Junwei Li6Yongxiang Yi7Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaFuqing Li Hualing TCM Clinic, 350000 Fuzhou, Fujian, ChinaClinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of neurology, Fujian Provincial Hospital, 350000 Fuzhou, Fujian, ChinaDepartment of Traditional Chinese Medicine, Fujian Medical University Union Hospital, 350000 Fuzhou, Fujian, ChinaDepartment of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Infectious Diseases, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaDepartment of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210003 Nanjing, Jiangsu, ChinaBackground: 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.https://www.imrpress.com/journal/FBL/27/1/10.31083/j.fbl2701025gigantolhepatocellular carcinomanetwork-based pharmacologicalmolecular dockinganti-hcc effect |
| spellingShingle | Shujie Li Hualing Li Dandan Yin Xiaojing Xue Xiaoling Chen Xiaoyue Li Junwei Li Yongxiang Yi Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments Frontiers in Bioscience-Landmark gigantol hepatocellular carcinoma network-based pharmacological molecular docking anti-hcc effect |
| title | Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments |
| title_full | Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments |
| title_fullStr | Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments |
| title_full_unstemmed | Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments |
| title_short | Effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network-based pharmacological approach and experiments |
| title_sort | effect of gigantol on the proliferation of hepatocellular carcinoma cells tested by a network based pharmacological approach and experiments |
| topic | gigantol hepatocellular carcinoma network-based pharmacological molecular docking anti-hcc effect |
| url | https://www.imrpress.com/journal/FBL/27/1/10.31083/j.fbl2701025 |
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