ArticlePloS one2016
P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- Vasoactivity of Rac GTPase, Cytohesin and Kinase Inhibitors in Renal Interlobar and Coronary Arteries Reveals Shared and Distinct Patterns of Inhibitory Effects in Vascular and Prostate Smooth Muscle Contraction.Pharmacology research & perspectives · 2025Article
- Tissue extracellular vesicles suppress neonatal cardiac regeneration: a Pak2-Erk1/2-mediated macrophage paracrine signaling.Acta biochimica et biophysica Sinica · 2025Article
- Developing prognostic models for cholesterol-related genes linked with immune infiltration in prostate cancer.Frontiers in genetics · 2025Article
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- PAK1-Dependent Regulation of Microtubule Organization and Spindle Migration Is Essential for the Metaphase I-Metaphase II Transition in Porcine Oocytes.Biomolecules · 2024Article
- FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003.Frontiers in pharmacology · 2023Article
- Inhibition of αNutrients · 2022Article
- The integrative analysis of competitive endogenous RNA regulatory networks in osteoporosis.Scientific reports · 2022Article
- Review
- Chemical carcinogen-induced rat mammary carcinogenesis is a potential model of p21-activated kinase positive female breast cancer.Physiological genomics · 2021Article
- Concentration-dependent alphaFrontiers in pharmacology · 2021Article
- Dysregulation of Rho GTPases in Human Cancers.Cancers · 2020Review
- Effect of PAK Inhibition on Cell Mechanics Depends on Rac1.Frontiers in cell and developmental biology · 2020Article
- Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance.Scientific reports · 2019Article
- Ghrelin Aggravates Prostate Enlargement in Rats with Testosterone-Induced Benign Prostatic Hyperplasia, Stromal Cell Proliferation, and Smooth Muscle Contraction in Human Prostate Tissues.Oxidative medicine and cellular longevity · 2019Article
- Inhibition of human prostate smooth muscle contraction by the LIM kinase inhibitors, SR7826 and LIMKi3.British journal of pharmacology · 2018Article
- The MAZ transcription factor is a downstream target of the oncoprotein Cyr61/CCN1 and promotes pancreatic cancer cell invasion via CRAF-ERK signaling.The Journal of biological chemistry · 2018Article
- Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-quinazoline-2,4-diamines as PAK4 Inhibitors with Potent A549 Cell Proliferation, Migration, and Invasion Inhibition Activity.Molecules (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate smooth muscle tone and hyperplastic growth are involved in the pathophysiology and treatment of male lower urinary tract symptoms (LUTS). Available drugs are characterized by limited efficacy. Patients' adherence is particularly low to combination therapies of 5α-reductase inhibitors and α1-adrenoceptor antagonists, which are supposed to target contraction and growth simultaneously. Consequently, molecular etiology of benign prostatic hyperplasia (BPH) and new compounds interfering with smooth muscle contraction or growth in the prostate are of high interest. Here, we studied effects of p21-activated kinase (PAK) inhibitors (FRAX486, IPA3) in hyperplastic human prostate tissues, and in stromal cells (WPMY-1). In hyperplastic prostate tissues, PAK1, -2, -4, and -6 may be constitutively expressed in catecholaminergic neurons, while PAK1 was detected in smooth muscle and WPMY-1 cells. Neurogenic contractions of prostate strips by electric field stimulation were significantly inhibited by high concentrations of FRAX486 (30 μM) or IPA3 (300 μM), while noradrenaline- and phenylephrine-induced contractions were not affected. FRAX486 (30 μM) inhibited endothelin-1- and -2-induced contractions. In WPMY-1 cells, FRAX486 or IPA3 (24 h) induced concentration-dependent (1-10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486 or IPA3. Cytotoxicity of FRAX486 and IPA3 in WPMY-1 cells was time- and concentration-dependent. Stimulation of WPMY-1 cells with endothelin-1 or dihydrotestosterone, but not noradrenaline induced PAK phosphorylation, indicating PAK activation by endothelin-1. Thus, PAK inhibitors may inhibit neurogenic and endothelin-induced smooth muscle contractions in the hyperplastic human prostate, and growth of stromal cells. Targeting prostate smooth muscle contraction and stromal growth at once by a single compound is principally possible, at least under experimental conditions.
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