Peroxisomal lipid metabolism inhibits Pimozide-induced cancer cell death by regulating ATP homeostasis.

ABSTRACT: Antipsychotic drugs have been shown to suppress tumor growth and induce cell death, but their clinical application remains limited. Pimozide, an FDA-approved antipsychotic, holds significant potential for cancer treatment. However, the mechanisms underlying tumor cell responses to Pimozide remain unclear. In this study, we identify a critical role for peroxisomes in mediating tumor cell resistance to Pimozide. Our findings demonstrate that Pimozide increases peroxisome numbers and that peroxisomal deficiency significantly enhances Pimozide-induced cell death. We show that peroxisomes mitigate Pimozide-induced apoptosis primarily through fatty acid oxidation and ether lipid synthesis, rather than reactive oxygen species (ROS) metabolism. Moreover, Pimozide treatment upregulates peroxisomal

SUBMITTER: Pan Z 

PROVIDER: S-EPMC12371041 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature