The immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide may exhibit therapeutic efficacy in the prostate. In lower urinary tract symptoms (LUTS), voiding and storage disorders may arise from benign prostate hyperplasia, or overactive bladder. While current therapeutic options target smooth muscle contraction or cell proliferation, side effects are mostly cardiovascular. Therefore, we investigated effects of IMiDs on human detrusor and porcine artery smooth muscle contraction, and growth-related functions in detrusor smooth muscle cells (HBdSMC).
Cell viability was assessed by CCK8, and apoptosis and cell death by flow cytometry in cultured HBdSMC. Contractions of human detrusor tissues and porcine interlobar and coronary arteries were induced by contractile agonists, or electric field stimulation (EFS) in the presence or absence of an IMID using an organ bath. Proliferation was assessed by EdU assay and colony formation, cytoskeletal organization by phalloidin staining, RESULTS: Depending on tissue type, IMiDs inhibited cholinergic contractions with varying degree, up to 50 %, while non-cholinergic contractions were inhibited up to 80 % and 60 % for U46619 and endothelin-1, respectively, and EFS-induced contractions up to 75 %. IMiDs reduced viable HBdSM cells in a time-dependent manner. Correspondingly, proliferation was reduced, without showing pro-apoptotic effects. In parallel, IMiDs induced cytoskeletal disorganization.
IMiDs exhibit regulatory functions in various smooth muscle-rich tissues, and of cell proliferation in the lower urinary tract. This points to a novel drug class effect for IMiDs, in which the molecular mechanisms of action of IMiDs merit further consideration for the application in LUTS.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024 Jul 08 [Epub ahead of print]
Alexander Tamalunas, Amin Wendt, Florian Springer, Victor Vigodski, Moritz Trieb, Nikolaus Eitelberger, Henrik Poth, Anna Ciotkowska, Beata Rutz, Sheng Hu, Heiko Schulz, Stephan Ledderose, Nina Rogenhofer, Thomas Kolben, Elfriede Nössner, Christian G Stief, Martin Hennenberg
Department of Urology, University Hospital Munich, LMU Munich, Munich, Germany; Immunoanalytics Research Group Tissue Control of Immunocytes, Helmholtz Center Munich, Munich, Germany. Electronic address: ., Department of Urology, University Hospital Munich, LMU Munich, Munich, Germany., Department of Pathology, University Hospital Munich, LMU Munich, Munich, Germany., Department of Obstetrics and Gynecology, University Hospital Munich, LMU Munich, Munich, Germany., Immunoanalytics Research Group Tissue Control of Immunocytes, Helmholtz Center Munich, Munich, Germany.