Journal of Developmental Medicine(Electronic Version)  2022, Vol. 10 Issue (4): 241-249 DOI: 10.3969/j.issn.2095-5340.2022.04.001 |
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| Study of the inhibitory effect of Prunellae Spica’s effective components on thyroid cancer in children |
| Chen Lei, Lu Zerong, Huang Yuqing, et al
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(1. Department of Pharmacy, Shenzhen Hospital ofGuangzhou University of Chinese Medicine (Futian), Guangdong, Shenzhen 518034, China; 2. FormulaPattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangdong, Guangzhou510632, China)
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Abstract 【Abstract】 Objective To explore the effective components of Prunellae Spica against thyroid cancer in children and its underlying mechanism. Method The candidate effective components and potential targets of Prunellae Spica against thyroid cancer in children were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) and GeneCards database. The drug-ingredient-target-disease network was constructed by Cytoscape software. The protein-protein interaction (PPI), gene ontology (GO) enrichment,and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment of potential targets were analyzed. Molecular docking was used to verify the combination between effective components and potential targets. The anti-proliferative effects of effective component on human papilloma-like thyroid cancer cells (TPC1) which were selected as the study objects were evaluated by cell counting kit (CCK)-8. The effects of effective component on cell cycle and cell apoptosis were detected by flow cytometry. The statistical analysis and drafting were conducted by GraphPad Prism 8.0 software. One-way analysis of variance (ANOVA) and t-test were applied as statistical approaches. Result Eleven candidate effective components against thyroid cancer in children and corresponding 166 potential targets were screened from Prunellae Spica. PPI, GO and KEGG analysis predicted that quercetin, luteolin, and kaempferol, the effective components of Prunellae Spica, might exert inhibitory effect by inhibiting AKT signaling pathway. The results of molecular docking demonstrated that the binding energy of quercetin, luteolin, and kaempferol to AKT (PDB ID: 4GV1) was -7.35, -7.17 and -7.32 kcal/mol respectively, indicating a good binding affinity and formation of stable complex. The results of CCK-8 assay indicated that quercetin displayed the most potent inhibitory effect against TPC1 among these three candidate components, with the half maximal inhibitory concentration (IC50) value of (19.4±4.8) μmol/L for 48 hours, whereas the IC50 value of luteolin was (64.8±7.7) μmol/L, and the IC50 value of kaempferol was greater than 100 μmol/L. After treatment with different concentrations of quercetin, the cell population in G2/M phase was (18.97±1.50) % in 50 μmol/L treatment group, compared with (12.88±1.33) % in
control group (P<0.01). The ratio of apoptotic cell was (30.77±4.52) % in 50 μmol/L treatment group, compared with (10.34±1.76) % in control group (P<0.001), in a concentration-dependent manner. The difference wasstatistically significant. Conclusion Quercetin, the effective component of Prunellae Spica, induced G2/Mcell cycle arrest and apoptosis in thyroid cancer TPC1 cells, which might be mediated by inhibition of AKTsignaling pathway.
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Received: 10 March 2022
Published: 29 July 2022
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