Network pharmacology and molecular docking studies of quercetin as a potential treatment for prostate cancer

Abstract

Prostate cancer is the second most prevalent malignancy worldwide, following lung cancer and in Africa, it is the most common cancer among men. Quercetin is a plant flavanoid and it has anti-inflammatory, antioxidant and anticancer properties have been extensively studied, however the molecular mechanisms underlying its chemopreventive effects are still poorly understood. In this study, the molecular targets and potential mechanisms underlying the action of quercetin as a therapeutic agent for prostate cancer were identified and validated via network pharmacology and molecular docking methods. The biological targets of quercetin against prostate cancer were obtained through database mining. Compound–disease target (C-D) networks were constructed, and targets were further analyzed using KEGG pathway analysis. Potent targets were retrieved from the compound–disease–pathway (C-D-P) and protein–protein interaction (PPI) networks. The binding affinities between quercetin and the potent targets were identified using molecular docking. The pathway enrichment analysis showed that prostate cancer associated targets were mainly associated with pathways such as 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 of molecular docking showed that quercetin can bind stably to with the key targets and KRAS had the least average binding affinity among the five ligand-target complexes. In conclusion, this study provided a novel approach to reveal the molecular targets and therapeutic mechanisms of quercetin on prostate cancer which will ease the future clinical application of quercetin in the treatment of prostate cancer.