Cholestane-3β,5α,6β-triol induces cancer cell death by activating GSDME-mediated pyroptosis.

ABSTRACT:

Background

Trihydroxysterols and their analogues accumulate in several pathologies, including neurodegenerative diseases, cancers, and atherosclerosis. Cholestane-3β,5α,6β-triol (CT), recognized as an apoptosis-inducing agent, also exhibits pro-inflammatory effects. Nevertheless, the mechanisms underlying CT-induced cytotoxicity and inflammation remain incompletely characterized.

Methods

RNA-sequencing (RNA-seq) analysis indicated CT can stimulate pro-inflammatory cytokine expression. We then employed multiple cell death inhibitors to confirm the predominant form of CT-induced cell death. Using combined chemical inhibition and genetic editing approaches, we established the relationship between caspase 3 activation, CT-mediated gasdermin E (GSDME) cleavage, and subsequent cel

SUBMITTER: Chen J 

PROVIDER: S-EPMC12592123 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature