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Inhibition of prostate smooth muscle contraction and prostate stromal cell growth by the inhibitors of R ac, NSC 23766 and EHT 1864
Author(s) -
Wang Y,
Kunit T,
Ciotkowska A,
Rutz B,
Schreiber A,
Strittmatter F,
Waidelich R,
Liu C,
Stief C G,
Gratzke C,
Hennenberg M
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13099
Subject(s) - calponin , stromal cell , prostate , hyperplasia , prostate cancer , cell growth , medicine , chemistry , endocrinology , cancer research , pathology , immunohistochemistry , cancer , biochemistry
Background and Purpose Medical therapy of lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH ) targets smooth muscle contraction in the prostate, or prostate growth. However, current therapeutic options are insufficient. Here, we investigated the role of R ac in the control of smooth muscle tone in human prostates and growth of prostate stromal cells. Experimental Approach Experiments were performed using human prostate tissues from radical prostatectomy and cultured stromal cells ( WPMY ‐1). Expression of R ac was examined by W estern blot and fluorescence staining. Effects of R ac inhibitors ( NSC 23766 and EHT 1864) on contractility were assessed in the organ bath. The effects of R ac inhibitors were assessed by pull‐down, cytotoxicity using a cell counting kit, cytoskeletal organization by phalloidin staining and cell growth using an 5‐ethynyl‐2′‐deoxyuridine assay. Key Results Expression of R ac1–3 was observed in prostate samples from each patient. Immunoreactivity for R ac1–3 was observed in the stroma, where it colocalized with the smooth muscle marker, calponin. NSC 23766 and EHT 1864 significantly reduced contractions of prostate strips induced by noradrenaline, phenylephrine or electrical field stimulation. NSC 23766 and EHT 1864 inhibited R ac activity in WPMY ‐1 cells. Survival of WPMY ‐1 cells ranged between 64 and 81% after incubation with NSC 23766 (50 or 100 μ M ) or EHT 1864 (25 μ M ) for 24 h. NSC 23766 and EHT 1864 induced cytoskeletal disorganization in WPMY ‐1 cells. Both inhibitors impaired the growth of WPMY ‐1 cells. Conclusions and Implications R ac may be a link connecting the control of prostate smooth muscle tone with proliferation of smooth muscle cells. Improvements in LUTS suggestive of BPH by R ac inhibitors appears possible.