Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Inflammation promotes prostate cancer (PCa) progression by creating a tumor-promoting microenvironment.
• NOD-like receptor protein 3 (NLRP3)-inflammasome activation, IL-1β secretion, and extracellular vesicles (EVs) are key contributors to this microenvironment.
• PCa progression is linked to constitutive inflammasome activation and reduced endogenous Natriuretic Peptides (NPs).

Purpose of the Study:

• To investigate the role of Natriuretic Peptides (NPs), specifically ANP and BNP, in modulating the inflammatory phenotype of prostate cancer (PCa) cells in vitro.
• To determine if exogenous ANP and BNP can inhibit inflammasome activation and IL-1β secretion in PCa models.

Main Methods:

• Utilized PNT2, LNCaP, and PC3 cell lines representing different PCa stages.
• Analyzed inflammasome activation and related pathways using Western blot.
• Quantified IL-1β secretion via ELISA.

Main Results:

• Prostate cancer progression correlates with constitutive inflammasome activation, elevated IL-1β secretion, and decreased endogenous NP expression.
• Exogenous ANP and BNP administration inhibited inflammasome activation and IL-1β maturation in PC3 cells and PC3-EVs-treated PNT2 cells.
• These inhibitory effects were mediated through p38-MAPK and ERK1/2-MAPK pathways, inducing NLRP3 phosphorylation.

Conclusions:

• Natriuretic Peptides (NPs) exert anti-inflammatory effects in prostate cancer by interfering with cell-specific signaling pathways, specifically through inflammasome phosphorylation.
• NPs demonstrate potential as a therapeutic strategy for PCa, warranting further investigation for drug repurposing.