Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Castration-resistant prostate cancer (CRPC) is an aggressive malignancy with limited treatment options.
• Androgen deprivation therapy (ADT) is a standard treatment, but resistance inevitably develops.
• Pyrimethamine, an antimalarial drug, shows potential antitumor activity, but its effect on prostate cancer is not well understood.

Purpose of the Study:

• To investigate the efficacy and mechanism of pyrimethamine in treating prostate cancer.
• To determine pyrimethamine's effects on prostate cancer cell proliferation, cell cycle, and apoptosis.
• To explore pyrimethamine's impact on the p38-NF-κB signaling pathway in prostate cancer.

Main Methods:

• In vitro studies using DU145 and PC3 metastatic prostate cancer cell lines.
• In vivo studies using xenograft models to assess tumor growth suppression.
• Analysis of cell proliferation, cell cycle progression, apoptosis, and p38-NF-κB pathway activity.

Main Results:

• Pyrimethamine significantly inhibited prostate cancer cell proliferation and induced S-phase cell cycle arrest.
• The drug promoted apoptosis in prostate cancer cells in vitro and suppressed tumor growth in vivo.
• Pyrimethamine was found to inhibit the p38-NF-κB axis, both in vitro and in vivo.

Conclusions:

• Pyrimethamine demonstrates significant antiproliferative and proapoptotic effects on prostate cancer cells.
• The drug acts by modulating cell cycle and intrinsic apoptotic signaling pathways.
• Pyrimethamine represents a novel therapeutic strategy for castration-resistant prostate cancer (CRPC) by targeting the p38-NF-κB axis.