Network pharmacology integrated molecular docking of fucoidan against oral cancer and in vitro evaluation- A study
Arul Jayanthi Antonisamy1, Karthikeyan Rajendran1, Premnath Dhanaraj2
1Department of Biotechnology, Mepco Schlenk Engineering College (Autonomous), Sivakasi, Tamil Nadu, India.
Abstract:
Oral cancer is a widespread health concern in rural India due to a lack of awareness, delayed diagnosis and limited access to affordable treatment options. The current chemotherapy has notable side effects, underscoring the need for new drug candidates with improved bioavailability and specificity. In this current research, fucoidan, a sulphated polysaccharide, was extracted from the brown algae Spatoglossum asperum, and shown to be cytotoxic in vitro against oral cancer cells (KB cell line) at an IC50 of 107.76 µg/ml, suggesting its potential as a drug candidate. This study further aimed to explore the potential therapeutic implications of fucoidan in managing oral cancer using network pharmacology. PharmMapper, Comparative Toxicogenomics Database and SuperPred were initially used to identify fucoidan protein targets. The identified targets were further screened against Gene Expression Omnibus (GSE23558, GSE25099 and GSE146483), OMIM, TCGA and GeneCards datasets to identify oral cancer-specific protein targets. The interactions between the selected proteins were visualised using STRING and Cytoscape. Subsequently, Database for Annotation, Visualization and Integrated Discovery was used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of candidate targets. The cancer-related network was assessed using CancerGeneNet, while life expectancy based on the expression of the top 10 CytoHubba ranked hub genes was evaluated using Kaplan-Meier plots. Finally, EGFR, AKT1, HSP90AA1 and SRC were selected for docking and molecular dynamics simulation with fucoidan, using Maestro and GROMACS, respectively.
Insights
Fucoidan from brown algae shows potential against oral cancer cells. Network pharmacology identified key targets, suggesting fucoidan as a promising therapeutic candidate for oral cancer management.
Area of Science:
- Marine natural products
- Computational pharmacology
- Oral oncology
Background:
- Oral cancer poses a significant health challenge, particularly in rural India, due to limited treatment access and awareness.
- Existing chemotherapy options for oral cancer have substantial side effects, necessitating novel therapeutic agents with enhanced specificity and bioavailability.
- Fucoidan, a sulfated polysaccharide from brown algae, exhibits cytotoxic effects against oral cancer cells in vitro.
Purpose of the Study:
- To investigate the therapeutic potential of fucoidan for oral cancer management.
- To identify fucoidan's protein targets and elucidate its mechanism of action using network pharmacology.
- To validate potential therapeutic targets through bioinformatics analysis and molecular simulations.
Main Methods:
- Fucoidan was extracted from *Spatoglossum asperum* and its cytotoxicity was assessed.
- Network pharmacology approaches, including PharmMapper, CTD, and SuperPred, were employed to identify fucoidan targets.
- Bioinformatics databases (GEO, OMIM, TCGA, GeneCards) and tools (STRING, Cytoscape, DAVID, KEGG, CancerGeneNet) were used for target validation and pathway analysis.
- Molecular docking and dynamics simulations were performed on key identified targets (EGFR, AKT1, HSP90AA1, SRC).
Main Results:
- Fucoidan demonstrated in vitro cytotoxicity against oral cancer cells (KB cell line) with an IC50 of 107.76 µg/ml.
- Network pharmacology identified potential protein targets for fucoidan, which were further refined using oral cancer-specific datasets.
- Pathway enrichment analysis highlighted key biological processes and pathways associated with fucoidan's action.
- Molecular simulations provided insights into the binding interactions of fucoidan with critical targets like EGFR, AKT1, HSP90AA1, and SRC.
Conclusions:
- Fucoidan extracted from *Spatoglossum asperum* exhibits promising anti-oral cancer activity.
- Network pharmacology and bioinformatics analyses reveal potential therapeutic targets and pathways for fucoidan in oral cancer.
- Fucoidan represents a potential lead compound for developing novel, targeted therapies for oral cancer, warranting further investigation.
