Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles.

ABSTRACT: Paraptosis is a distinct form of programmed cell death characterized by cytoplasmic vacuolization, mitochondrial swelling, and endoplasmic reticulum (ER) dilation, offering an alternative to apoptosis for therapeutic applications. In this study, we identified a hemicyanine derivative that is a potent paraptosis inducer in two cancer cell lines. This compound triggers hallmark paraptotic features, including ER swelling, mitochondrial morphological changes, increased superoxide production, and caspase-independent cell death. This activity is dependent on the ability of the probe to modify thiols covalently. Proteomic analysis using a biotinylated, activity-based probe revealed Sec23 homologue A and GDP-dissociation inhibitor alpha as potential targets implicated in paraptosis activation. Thi

SUBMITTER: Tamez-Fernandez JF 

PROVIDER: S-EPMC12426919 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature