Fig. 2: σ1R antagonists impair cancer stem cell expansion in vitro.
From: Integrated control of cancer stemness by σ1 receptor in advanced prostate cancer
A Chemical structures of WMS 26-09 and WMS 26-10. Compounds are shown as colored sticks-and-ball structures. B Overlay of WMS 26-09 (tan) against WMS 26-10 (rosy brown) binding to σ1R. The structure of σ1R was obtained from the RCSB Protein Data Bank (PDB ID 5HK1). Estimated free energy of binding (ΔGbind) for WMS 26-09 and WMS 26-10 by the Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) approach were −11.22 kcal/mol and −10.76 kcal/mol, respectively. Tumor-sphere (C) and proliferation (D) of DU145 cells incubated with σ1R antagonists WMS 26-09 and WMS 26-10. E Tumor-sphere formation of pre-selected DU145 stem-like cells treated with WMS 26-09. F Tumor-sphere formation by DU145 cells treated with WMS 26-09 (10 µM) during the first generation (G1) and after replating for the second generation (G2) in drug-free medium. G, H Tumor-sphere formation (G) and proliferation (H) of VCaP cells treated with σ1R antagonists. I, J Tumor-sphere formation (I) and proliferation (J) of H660 cells treated with σ1R antagonists. K, L Tumor-sphere and prostate-sphere formation (K) and proliferation (L) of DU145, 22Rv1, VCaP, and RWPE-1 exposed to PRE-084 (10 µM). Data are mean ± SD; *P < 0.01 by t-test and ANOVA.
