Phenyl-methylene hydantoins alter CD44-specific ligand binding of benign and malignant prostate cells and suppress...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Dysregulated CD44 expression, particularly the splice variant CD44v7-10, is implicated in prostate cancer (PCa) progression and invasion.
• CD44 standard (CD44s) is typically downregulated in PCa, while CD44v7-10 facilitates fibronectin binding and enhances invasiveness.
• Phenyl-methylene hydantoin (PMH) and S-ethyl PMH (S-PMH) are compounds with reported anti-cancer properties, including reduced invasion and growth.

Purpose of the Study:

• To investigate the effects of PMH and S-PMH on prostate cancer cell adhesion and CD44 expression.
• To determine the molecular mechanisms by which these compounds influence cell adhesion to hyaluronan and fibronectin.

Main Methods:

• Benign (BPH-1) and malignant (PC-3M) prostate cells were treated with PMH or S-PMH.
• Cell adhesion assays were performed using hyaluronan and fibronectin as substrates.
• Western blot analysis and real-time RT-PCR were used to quantify CD44 total, CD44v7-10, beta-catenin, and beta1-integrin expression.

Main Results:

• PMH and S-PMH significantly decreased prostate cancer cell adhesion to both hyaluronan and fibronectin.
• Both compounds reduced mRNA expression of total CD44 and CD44v7-10.
• S-PMH decreased total CD44 protein, while both compounds reduced CD44v7-10 protein levels, beta-catenin, and slightly affected beta1-integrin.

Conclusions:

• PMH and S-PMH effectively reduce prostate cancer cell adhesion by modulating CD44 expression.
• Decreased adhesion to hyaluronan is associated with reduced CD44s, while reduced fibronectin adhesion correlates with decreased CD44v7-10.
• These findings suggest PMH and S-PMH as potential therapeutic agents for prostate cancer by targeting CD44-mediated cell adhesion and invasion.