Repurposing thioridazine for inducing immunogenic cell death in colorectal cancer via eIF2α/ATF4/CHOP and secretory autophagy pathways.

ABSTRACT:

Background

Colorectal cancer (CRC) is a highly prevalent cancer type with limited targeted therapies available and 5-year survival rate, particularly for late-stage patients. There have been numerous attempts to repurpose drugs to tackle this problem. It has been reported that autophagy inducers could augment the effect of certain chemotherapeutic agents by enhancing immunogenic cell death (ICD).

Methods

In this study, we employed bioinformatics tools to identify thioridazine (THD), an antipsychotic drug, and found that it could induce autophagy and ICD in CRC. Then in vitro and in vivo experiments were performed to further elucidate the molecular mechanism of THD in CRC.

Results

THD was found to induce endoplasmic reticulum (ER) stress in CRC cells by activating the

SUBMITTER: Tran TH 

PROVIDER: S-EPMC10364410 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature