Abstract
Globally, the prevalence of prostate cancer is only the second to lung cancer. In Africa however, the commonest cancer among men is cancer of the prostate. The use of natural compounds from plants such as quercetin is being explored as a potential cure. Quercetin is a plant-based flavonoid that has anti-inflammatory, antioxidant and anticancer properties. Although quercetin has been extensively studied, its chemo preventive mode of action is not well-understood. The molecular targets and potential mechanisms underlying the action of quercetin against prostate cancer were identified and validated using network pharmacology and molecular docking methods. The biological targets of quercetin and targets associated with prostate cancer were obtained through database mining. Overlapping targets associated with quercetin and prostate cancer were identified and used to construct a compound-disease target (C-D) network and the targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction analysis (PPI). A disease target- pathway network was constructed and then merged with C-D network to form a compound-disease_target-pathway (C-D-P) network. Hub targets were obtained from the C-D-P and PPI networks. The binding affinities between quercetin and the retrieved hub targets were identified. Pathway enrichment analysis showed that prostate cancer associated quercetin targets were mainly linked with pathways such as the cancer signaling pathways (HIF-1 and ErbB) and hepatitis B. Basing on the PPI and C-D-P network analysis STAT3, TP53, MAPK1, MAPK3 and KRAS were identified as the main targets and were subjected to molecular docking. The results showed quercetin's ability to stably bind to the key targets. In conclusion, this study showed the potential molecular targets and mode of action of quercetin in prostate cancer treatment. This can potentially inform the future use of quercetin in the treatment of prostate cancer.
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