Investigating Drug-Target Interactions of Piperine in Prostate Cancer using Network Pharmacology and Docking studies

Abstract

The prostate cancer is the third-leading cause of death worldwide. As per therapeutic medicines, piperine plays a key role in anti-inflammatory and anti-cancer activities. A comprehensive investigation was conducted to determine the possible protein targets of piperine in cancer by employing network pharmacology and molecular docking methods. The PubChem, ChEMBL, STITCH andCTD databases were used for integrated prediction of piperine targets in cancer followed by network building, network architecture, gene ontology (GO), pathway enrichment and molecular docking in the present investigation. According to a functional annotation study, piperine has a list of potential cancer targets (10 targets). The unique target of piperine was identified based on topological evaluation by finding significant closeness/hub node AKT1 (RAC-alpha serine/threonine-protein kinase). PANTHER gene set analysis was also utilized to identify biologically significant pathways in the top genes involved. High efficiency and scalability of molecular docking were used to verify the identified targets. AKT1 docking findings with piperine showed the highest binding affinity, hydrogen bonds and good inhibitory effect compared to standard flutamide. AKT1 identified by the network pharmacological approach might be a potential target of piperine to prevent prostate cancer based on the molecular interaction.