Pyrimethamine Triggers the Apoptotic Pathway in Mucoepidermoid Carcinoma in Cell-Based Models

Area of Science:

• Oncology
• Drug Repurposing
• Molecular Biology

Background:

• Mucoepidermoid carcinoma (MEC) is the most common salivary gland cancer.
• High-grade MEC at diagnosis has a poor prognosis, necessitating novel therapeutic agents.
• Investigating pyrimethamine (PYR), an antiparasitic drug, as a potential MEC treatment.

Purpose of the Study:

• To evaluate the antineoplastic efficacy of pyrimethamine (PYR) against human mucoepidermoid carcinoma (MEC).
• To explore the potential of repurposing the antiparasitic drug pyrimethamine for MEC treatment.

Main Methods:

• Assessed antiproliferative effects using trypan blue exclusion, CCK-8, and live/dead assays.
• Confirmed PYR-induced apoptosis via DAPI staining, cell cycle analysis, and Annexin V/PI staining.
• Measured cleaved caspase 8 and Mcl-1 expression changes using Western blot and 3D culture models.

Main Results:

• Pyrimethamine (PYR) induced apoptotic cell death in the YD-15 high-grade MEC cell line.
• Apoptosis was evidenced by Mcl-1 proteasomal degradation and increased cleaved caspase 8 expression.
• PYR demonstrated efficacy in a three-dimensional culture system.

Conclusions:

• Pyrimethamine (PYR) effectively targets human MEC by inducing apoptosis.
• PYR activates both intrinsic and extrinsic apoptotic pathways in MEC cells.
• Repurposing PYR offers a potential therapeutic strategy for high-grade MEC.