Rosdi, Norsyasya Adriana (2021) Evaluation of the Effect of Lemongrass and Gemcitabine Combination Treatment on Pancreatic Cancer through Network Pharmacology: Findings of Bioinformatics Analyses. [Project Paper] (Submitted)
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Abstract
Pancreatic cancer has contributed to a poor prognosis in cancer diagnosis as it is often detected at the more advanced stage. Gemcitabine (GEM) has replaced fluorouracil as the first-line chemotherapy drug for pancreatic cancer since 1997. However, the 5-year survival rate of a pancreatic cancer patient has not yet improved and GEM resistance is widespread. Lemongrass, commonly found in the region with lower incidence, was observed to have a therapeutic value for many kinds of cancers including pancreatic cancer. Therefore, it is assumed that lemongrass and GEM may effectively manage pancreatic cancer; however, their combined effect is still unclear. Objective: This study aims to evaluate the combined effect of lemongrass and GEM on pancreatic cancer through network pharmacology. Methodology: Lemongrass bioactive compounds were screened from Traditional Chinese Medicine Systems Pharmacology and Traditional Chinese Medicine Integrated Database. Potential gene targets of the compounds and GEM were predicted through Disease Gene Interaction database, DrugBank, Comparative Toxicogenomics Database, Swiss Target Prediction, and Chemmapper databases. Pancreatic cancer genes were retrieved from MalaCards and Online Mendelian Inheritance in Man databases. The intersection genes between lemongrass bioactive compound, GEM and pancreatic cancer were created using the online Venn Diagram tool. The STRING database and Cytoscape software were used to construct protein-protein interaction and compound-target-pathway network, respectively. The DAVID bioinformatics tool was utilized to conduct gene ontology (GO) and pathway analysis. Results: As a result, there were 27 compounds in lemongrass, however only luteolin (LUT) that met the drug screening requirements and were selected as the bioactive compound. LUT has a total of 296 potential gene targets, with 67 shared with pancreatic cancer while GEM has a total of 352 potential gene targets, with 89 shared with pancreatic cancer. Among those, several genes including TP53, AKT1, VEGFA, EGFR, MYC, CCND1, STAT3, PTEN, CASP3, MAPK3, and BCL2L1 genes were identified as the hub genes with high biological relevance in pancreatic cancer. The GO and pathway analysis indicated that the combination treatment mainly acts on several cancer-related pathways, including pancreatic cancer, through apoptotic and cell proliferation regulation. Discussion: Hub genes are highly interconnected with nodes in the network and they were functionally enriched in multiple pathways. Therefore, it is believed that the potential mechanism is a synergy of multi-target and multi-pathway efforts. Conclusion: Since GEM treatment alone was commonly associated with the increased resistance development, this in silico study was conducted and has revealed that the effect of GEM in the pancreatic cancer treatment will be enhanced when in combination with LUT. Also, this study might provide an insight into lemongrass and GEM combination treatment against pancreatic cancer. However, further in vitro and in vivo experimental validation is needed to verify these computational findings.
| Item Type: | Project Paper |
|---|---|
| Faculty: | Faculty of Medicine and Health Science |
| Depositing User: | Ms. Nor Safa'aton Saidin |
| Date Deposited: | 22 Aug 2023 07:50 |
| Last Modified: | 22 Aug 2023 07:50 |
| URI: | http://psaspb.upm.edu.my/id/eprint/1046 |
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