Fig 1: In silico molecular docking of manzamine A (MA) with E2F8 using BIOVIA, Dassault Systèmes, Discovery Studio Visualizer v21.1.0.20298. (A) MA (red) and DNA (yellow) is shown in the DNA binding domain (DBD) of E2F8 (PDB ID: 4YO2), which is located between DBD1 (blue) and DBD2 (pink), (B) DNA nucleotides (blue) and (C) MA (red) interactions with the amino acid residues of E2F8. (D) MA‐targeted inhibition of E2F8 in LNCaP and 22Rv1 cells, and the data were repeated twice with similar results. (E) siRNA‐directed E2F8 knockdown and repression of androgen receptor (AR) and its variant (V7) protein (upper panel) and AR‐regulated genes (lower panel). (F) Inhibition of luciferase reporter activity of human AR‐luc (pGL1.8 and pGL2.4) in AR‐positive 22Rv1 cells following siRNA‐directed E2F8 knockdown for 48 h. The bar graphs in E and F represent mean ± SE from three (n = 3) independent experiments with significance level at **P < 0.01 using Welch t‐test analysis.