α-NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase-4 pathway

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Chemotherapy resistance is a major challenge in treating epithelial ovarian cancer (EOC).
• Identifying novel antitumor agents is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate the antitumor effects of the novel molecule 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA) on epithelial ovarian cancer (EOC) cells.
• To elucidate the mechanism by which α-NETA induces cell death in EOC.

Main Methods:

• Cell Counting Kit-8 assay and fluorescence-activated cell sorting (FACS) to assess cell viability.
• Electron microscopy to examine cellular morphology.
• Western blotting to analyze the expression of pyroptosis-associated molecules (caspase-4 and GSDMD).
• Gene knockdown experiments to confirm the involvement of the pyroptosis pathway.
• In vivo studies using mouse models to evaluate tumor reduction.

Main Results:

• α-NETA induced cell death in multiple EOC cell lines (Ho8910, Ho8910PM, A2780).
• Morphological analysis confirmed pyroptosis characterized by microbubble formation.
• α-NETA significantly upregulated caspase-4 and GSDMD expression.
• Knockdown of caspase-4 or GSDMD abrogated α-NETA's cell-killing effect.
• In vivo, α-NETA treatment markedly reduced EOC tumor size.

Conclusions:

• α-NETA induces pyroptosis in epithelial ovarian cancer cells via the GSDMD/caspase-4 pathway.
• α-NETA demonstrates significant antitumor activity in both in vitro and in vivo models.
• α-NETA represents a promising novel antitumor agent or lead compound for EOC chemotherapy.