Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2

British Journal of Pharmacology
Yiming WangM Hennenberg

Abstract

In benign prostatic hyperplasia, increased prostate smooth muscle tone and prostate volume may contribute alone or together to urethral obstruction and voiding symptoms. Consequently, it is assumed there is a connection between smooth muscle tone and growth in the prostate, but any molecular basis for this is poorly understood. Here, we examined effects of Src family kinase (SFK) inhibitors on prostate contraction and growth of stromal cells. SFK inhibitors, AZM475271 and PP2, were applied to human prostate tissues to assess effects on smooth muscle contraction, and to cultured stromal (WPMY-1) and c-Src-deficient cells to examine effects on proliferation, actin organization and viability. SFKs were detected by real time PCR, western blot and immunofluorescence in human prostate tissues, some being located to smooth muscle cells. AZM475271 (10 μM) and PP2 (10 μM) inhibited SFK in prostate tissues and WPMY-1 cells. Both inhibitors reduced α1 -adrenoceptor-mediated and neurogenic contraction of prostate strips. This may result from cytoskeletal deorganization, which was observed in response to AZM475271 and PP2 in WPMY-1 cells by staining of actin filaments with phalloidin. This was paralleled by reduced proliferation of wildtype...Continue Reading

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Citations

Mar 21, 2017·European Journal of Pharmacology·Martin HennenbergChristian Gratzke
Mar 27, 2018·British Journal of Pharmacology·Qingfeng YuMartin Hennenberg
Jul 3, 2018·Frontiers in Physiology·Martin HennenbergChristian Gratzke
Feb 13, 2017·Pflügers Archiv : European journal of physiology·Olga ZavaritskayaRudolf Schubert
Jul 17, 2020·Cancers·Francesco BonolloSofia Karkampouna

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