A novel small molecule NJH-13 induces pyroptosis via the Ca²⁺ driven AKT-FOXO1-GSDME signaling pathway in NSCLC by targeting TRPV5.

ABSTRACT:

Introduction

Pyroptosis represents a mode of programmed necrotic cell death (PCD), mediated by members of gasdermin family (GSDMs), such as GSDME. It is emerging as a promising approach for combating cancer. Notably, GSDME is the key modulator for the switch between apoptosis and pyroptosis in cells. However, GSDME is often downregulated in many malignancies, including lung adenocarcinoma.

Objective

To identify novel pyroptosis inducers in non-small cell lung cancer (NSCLC) and dissect the underlying mechanism.

Methods

Pyroptosis was examined by live cell imaging, PI/Hoechst/Annexin V staining, LDH release assay, ELISA, and western blot assays. DARTS, CETSA, molecular docking was used to identify the target of NJH-13. RNA-seq, qPCR, chromatin immunoprecipitation (ChIP

SUBMITTER: Dong X 

PROVIDER: S-EPMC12627346 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature