Devazepide, a nonpeptide antagonist of CCK receptor, induces cell apoptosis and inhibits contraction in human prostatic stromal myofibroblasts

Human prostatic stromal myofibroblasts have been shown to be related to lower urinary tract symptoms (LUTS) in aging men. Devazepide, also known as a nonpeptide antagonist of CCK receptor, has been found to inhibit the proliferation in tumor cells. Here, we aim to investigate the effects of Devazepide on growth and contraction ability in human prostatic stromal WPMY-1 myofibroblasts. Human prostatic stromal WPMY-1 myofibroblasts were treated with various concentrations of Devazepide. The cell viability was determined by WST-8 assay. TUNEL assay and Annexin-V/Propidium iodide (PI) staining were performed to determine cell apoptosis. Expression levels of cleaved Caspase-3 and cleaved Caspase-9 were examined by Western blot. Contraction ability in WPMY-1 cells was evaluated by collagen gel contraction assay. We found that cell viability of WPMY-1 cells was significantly inhibited in the presence of Devazepide. Devazepide inhibited growth of WPMY-1 cells in a dose and time-dependent manner. In addition, Devazepide could significantly induce G2/M cell cycle arrest and apoptosis in WPMY-1 cells. Increased expression levels of cleaved Caspase-3 and Caspase-9 proteins were found in Devazepide-treated WPMY-1 cells. Collagen gel contraction assay further showed that Devazepide could inhibit contraction ability of WPMY-1 cells, which might be associated with growth inhibition and decreased expression levels of Col1A1 and Col1A2 in WPMY1 cells. Taken together, Devazepide could inhibit in vitro growth and contraction ability in human prostatic stromal myofibroblasts, which might be a novel therapeutic target of LUTS in aging men.