Comprehensive serum metabolomics and network analysis to reveal the mechanism of gypenosides in treating lung cancer and enhancing the pharmacological effects of cisplatin

Qi, Yan-Shuang; Xiao, Man-Yu; Xie, Peng; Xie, Jinbo; Guo, Mei; Li, Fangfang; Piao, Xiang‐Lan

doi:10.3389/fphar.2022.1070948

Cited by 2 publications

(1 citation statement)

References 36 publications

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“…The intersection targets were integrated into the STRING database ( https://string-db.org/ ) to obtain information on their protein–protein interaction (PPI) network [ 12 ]. We established the screening parameters for the organism as "Homo sapiens" with a minimum required interaction score of "highest confidence (0.9)".…”

Section: Methodsmentioning

confidence: 99%

Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma

Wang,

Liu,

Guo

2023

BMC Complement Med Ther

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Background An anti-tumour activity has been demonstrated for α-solanine, a bioactive compound extracted from the traditional Chinese herb Solanum nigrum L. However, its efficacy in the treatment of gliomas and the underlying mechanisms remain unclear. The aim of this study was to investigate the inhibitory effects of α-solanine on glioma and elucidate its mechanisms and targets using network pharmacology, molecular docking, and molecular biology experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to predict the potential targets of α-solanine. GeneCards was used to gather glioma-related targets, and the STRING online database was used to analyze protein–protein interaction (PPI) networks for the shared targets. Hub genes were identified from the resulting PPI network and further investigated using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, prognostic and gene set enrichment analyses (GSEA) were carried out to identify potential therapeutic targets and their underlying mechanisms of action in relation to the prognosis of gliomas. In vitro experiments were conducted to verify the findings from the network pharmacology analysis. Results A total of 289 α-solanine targets and 1149 glioma-related targets were screened, of which 78 were common targets. 11 hub genes were obtained, including SRC, HRAS, HSP90AA1, IGF1, MAPK1, MAPK14, KDR, STAT1, JAK2, MAP2K1, and IGF1R. The GO and KEGG pathway analyses unveiled that α-solanine was strongly associated with several signaling pathways, including positive regulation of MAP kinase activity and PI3K-Akt. Moreover, α-solanine (10 µM and 15 µM) inhibited the proliferation and migration but promoted the apoptosis of glioma cells. Finally, STAT1 was identified as a potential mediator of the effect of α-solanine on glioma prognosis. Conclusion α-Solanine can inhibit the proliferation and migration of gliomas by regulating multiple targets and signalling pathways. These findings lay the foundation for the creation of innovative clinical anti-glioma agents.

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Section: Methodsmentioning

confidence: 99%

Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma

Wang,

Liu,

Guo

2023

BMC Complement Med Ther

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Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma

Mohd,

Michniak-Kohn

2024

Antioxidants

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Combining anti-cancer agents in cancer therapies is becoming increasingly common because of their improved efficacy, reduced toxicity, and decreased risk of resistance development. Melanoma, a highly aggressive form of skin cancer characterized by limited treatment options due to chemoresistance, poses a considerable challenge for effective management. Here, we test the hypothesis that dietary supplements such as thymoquinone (TQ) and curcumin (CU) cooperatively modulate cancer-associated cellular mechanisms to inhibit melanoma progression. Through a series of in vitro experiments utilizing the A375 melanoma cell line, including assessments of cell viability, apoptosis, multicellular tumor spheroid models, reactive oxygen species (ROS) quantification, metabolomics analysis, and RNA sequencing, we established that the combined application of TQ and CU exhibited superior anti-tumor effects compared to their individual use. Our results indicate that the combination treatment significantly inhibited cell viability and induced apoptosis more effectively than either agent alone, with optimal synergy observed at concentrations of 25 µM CU and 10 µM TQ against A375 cells. Additionally, the combination treatment markedly elevated ROS levels, selectively activating the mitochondrial apoptotic pathway via caspase-9. Differential gene expression analysis further revealed a unique synergistic effect of the combination treatment, with enhanced regulation of genes related to oxidative stress and apoptosis. Notably, pathways such as mitochondrial apoptotic signaling and redox homeostasis were more effectively influenced by the combination, with genes such as GPX3, CYP4F11, and HSPB8 cooperatively regulated. Overall, the findings suggest that, in combination, TQ and CU acts synergistically against melanoma; however, further experimental and clinical studies are required to confirm its therapeutic potential.

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Comprehensive serum metabolomics and network analysis to reveal the mechanism of gypenosides in treating lung cancer and enhancing the pharmacological effects of cisplatin

Cited by 2 publications

References 36 publications

Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma

Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma

Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma

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