Screening anticancer peptides performance in organotypic prostate tumor-stroma 3D models.

Area of Science:

• Oncology
• Biochemistry
• Drug Discovery

Background:

• Prostate cancer (PCa) remains a significant therapeutic challenge.
• Anticancer peptides offer novel strategies by disrupting protein-protein interactions.
• Targeting protein phosphatase 1 (PP1) complexes is a promising approach for cancer therapy.

Purpose of the Study:

• To evaluate the tumor-suppressive activity of the CAVPENET peptide in a 3D prostate cancer model.
• To assess CAVPENET's efficacy in a more physiologically relevant preclinical context.
• To investigate CAVPENET's specific effects on prostate cancer cells versus cancer-associated fibroblasts.

Main Methods:

• Development of a 3D physiomimetic human prostate cancer/cancer-associated fibroblast heterotypic spheroid model.
• Incubation of the 3D model with CAVPENET peptide.
• Assessment of spheroid growth, morphology, and cellular viability.
• Evaluation of CAVPENET's effect on monotypic cancer-associated fibroblast spheroids.

Main Results:

• The 3D heterotypic spheroid model exhibited in vivo-like tumor characteristics, including growth and increased cellular density.
• CAVPENET treatment significantly decreased prostate cancer spheroid growth and viability.
• CAVPENET did not affect the growth of cancer-associated fibroblast monotypic spheroids at the tested concentration (20 μM).

Conclusions:

• 3D heterotypic models are relevant for evaluating anticancer therapeutics.
• CAVPENET peptide demonstrates significant therapeutic potential for prostate cancer.
• CAVPENET selectively targets prostate cancer cells within a complex tumor microenvironment.