Deciphering the anti-prostate potentials of n-hexane fraction of berries of Solanum aculeastrum Dunal through in silico and in vitro evaluation

The study investigated antiprostatic effects of n-hexane fraction of S. aculeastrum Dunal berries (HFSADB) against benign prostatic hyperplasia (BPH) and prostate cancer (PC). Using Swiss ADME and pKCSM tools, drug candidates were obtained from HFSADB. Using BindingDB, Swiss Target Prediction and DisGeNET databases, compounds, and disease targets for BPH and PC were identified. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict mechanisms and pathways of interactions between compounds and target genes, respectively. Molecular docking was done using VINA tool. Antiproliferative activity and gene expression analysis of HFSADB were conducted using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) bioassay and RT-qPCR respectively, and data analyzed using Graph Pad Prism (version 8.4). Three molecules [(-)-cis-.beta.-Elemene; beta-Humulene; and Cadina-1(10),4-diene] were identified as drug candidates. Key targets include NCOA3, ESR2, PPARA, amongst others. GO analysis revealed key targets were mainly enriched in 327 biological processes (BP) terms, 43 molecular function (MF) terms and 5 cellular components (CC) terms (p < 0.05), while KEGG analysis revealed pathways in cancer, PPAR signaling pathway amongst others as primarily associated pathways. Docking analysis revealed two of the compounds [(-)-cis-.beta.-Elemene; and Cadina-1(10),4-diene] demonstrated strong binding affinity with PTGS2 and CYP19A1 target genes. HFSADB significantly (p < 0.0001) inhibited growth of DU-145 cells with IC₅₀ value and selectivity index of 5.478 μg/ml and 10.67, respectively, while sparing Vero CCL-81 cells. Significant (p < 0.0001) downregulation of PTGS2 and BCL-2 were observed in treated DU-145 cells compared to control. HFSADB demonstrated antiprostate activities.