AUTHOR=Zheng Yuanyuan , Yang Wenjuan , Jia Yewei , Ji Jie , Wu Liwei , Feng Jiao , Li Yan , Cheng Ziqi , Zhang Jie , Li Jingjing , Dai Weiqi , Xu Xuanfu , Wu Jianye , Zhou Yingqun , Guo Chuanyong 

TITLE=Promotion of colorectal cancer cell death by ezetimibe via mTOR signaling-dependent mitochondrial dysfunction

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1081980

DOI=10.3389/fphar.2023.1081980

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Colorectal cancer (CRC) is the fourth most common cancer worldwide, with high morbidity and mortality rates. In recent years, high-fat diet has been shown to increase CRC morbidity, highlighting the possibility of the application of hypolipidemic drugs for CRC treatment. In this study, we preliminarily evaluated the effects and mechnisms of ezetimibe against CRC through the blockage of lipid absorption in small intesine.</p><p><bold>Methods:</bold> In this study, CRC cell proliferation, invasion, apoptosis, and autophagy were evaluated using cellular and molecular assays. Fluorescent microscopy, and a flow cytometric assay were used to assess mitochondrial activity <italic>in vitro</italic>. A subcutaneous xenograft mouse model was used to evaluate the effects of ezetimibe <italic>in vivo</italic>.</p><p><bold>Results:</bold> We found that ezetimibe inhibited CRC cell proliferation, and migration, and facilitated autophage-associated apoptosis in HCT116 and Caco2 cells. Ezetimibe-induced mitochondrial dysfunction in CRC cells was found to be correlated with mTOR signaling activity.</p><p><bold>Discussion:</bold> Ezetimibe exhibits effects against CRC through the promotion of cancer cell death <italic>via</italic> mTOR signaling-dependent mitochondrial dysfunction, highlighting its potential value in CRC therapy.</p>