Sahruddin, Nursaffa Alisya (2021) A network pharmacology-based investigation on the potential effect of moringa aleifera and gemcitabine combination against pancreatic cancer. [Project Paper] (Submitted)
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Abstract
Pancreatic cancer is lethal and often considered as metastatic disease by the time of diagnosis as the signs and symptoms are difficult to detect. Gemcitabine (GEM) is the first-line chemotherapy drug against patients with advanced pancreatic cancer. Moringa oleifera (MO), a well-known Ayurvedic Indian medicine which is commonly found in India, Africa and Southeast Asia has exhibited various biological activity including anti-cancer effects, particularly on the pancreatic cancer cells. However, the effectiveness of MO and GEM combination against pancreatic cancer has yet to be explored. Objective: This study aims to evaluate the potential effect of MO together with GEM against pancreatic cancer by the integration of network pharmacology. Methodology: Traditional Chinese Medicine System Pharmacology, Traditional Chinese Medicine Integrated Database and PubMed databases were used to identify and screen the bioactive compounds in MO. Target genes of MO and GEM were predicted through Drug Gene Interaction Database, Comparative Toxicogenomics Database, and DrugBank databases. Pancreatic cancer genes were collected from Online Mendelian Inheritance in Man and MalaCards databases. Venn diagrams were constructed to identify pancreatic cancer-related target genes using Bioinformatics and Evolutionary Genomics tools. Protein-protein interaction (PPI) and compound-target-pathway network were established via STRING and Cytoscape, respectively. Gene ontology (GO) and pathway enrichment analysis were conducted using DAVID Bioinformatic Tools. Results: A total of 32 compounds have been identified in MO. Catechin, kaempferol, quercetin and epicatechin that met the drug screening requirements and 3 additional compounds- glucomoringin, glucoraphanin and moringinine were identified as bioactive compounds. Catechin was found to be the main hub compound in MO. There are 1092, 352 and 421 target genes were found in MO, GEM and pancreatic cancer, respectively. The Venn diagram revealed 5 intersections between the combination of MO and GEM. Among those intersections, 4 intersections were investigated which are GEM-, MO-, MO+GEM- and shared biotargets-intersections against pancreatic cancer. The studied compounds stimulate 4 hub genes from PPI network, which include TP53, AKT1, VEGFA and CCND1 in targeting pancreatic cancer. Also, 2 hub genes were identified including CASP3 and BCL2L1 which may represent the new targets against pancreatic cancer as they are not targeted by MO or GEM alone. GO and pathway analysis revealed that MO and GEM combination was mainly associated with cancer including pancreatic cancer through regulation of apoptosis and cell proliferation. Discussion: This is the first network pharmacology study that predict the target genes of the bioactive compounds of MO in combination with GEM and theoretically evaluate their effects against pancreatic cancer. Hub genes play a crucial role within the network with high biological importance and significantly enriched in multiple pathways. Thus, this study has revealed the multi-compounds, multi-targets and multi-pathways of MO and GEM combination against pancreatic cancer. Conclusion: To conclude, this in silico study suggested that the combination therapy of MO bioactive compounds and GEM synergistically enhance the effect in pancreatic cancer treatment. However, further experimental research and subsequent clinical applications are needed to validate these findings.
| Item Type: | Project Paper |
|---|---|
| Faculty: | Faculty of Medicine and Health Science |
| Depositing User: | Ms. Nor Safa'aton Saidin |
| Date Deposited: | 22 Aug 2023 07:51 |
| Last Modified: | 22 Aug 2023 07:51 |
| URI: | http://psaspb.upm.edu.my/id/eprint/1084 |
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