The role of the natural compound naringenin in AMPK-mitochondria modulation and colorectal cancer inhibition

作者：Dan Wang, Yue Zhou, Yue Zhou, Li Hua, Meichun Hu, Ni Zhu, Yifei Liu, Yanhong Zhou, Yanhong Zhou · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.155786 · 被引用次数：30 · 研究领域：Metabolism, Diabetes, and Cancer、Cancer, Hypoxia, and Metabolism、Flavonoids in Medical Research

BACKGROUND: Although AMP-activated protein kinase (AMPK) has been extensively studied in cellular processes, the understanding of its substrates, downstream functions, contributions to cell fate and colorectal cancer (CRC) progression remains incomplete. PURPOSE: The aim of this study was to investigate the effects and mechanisms of naringenin on CRC. METHODS: The biological and cellular properties of naringenin and its anticancer activity were evaluated in CRC. In addition, the effect of combined treatment with naringenin and 5-fluorouracil on tumor growth in vitro and in vivo was evaluated. RESULTS: The present study found that naringenin inhibits the proliferation of CRC and promote its apoptosis. Compared with the naringenin group, naringenin combined with 5-fluorouracil had significant effect on inhibiting cell proliferation and promoting its apoptosis. It is showed that naringenin activates AMPK phosphorylation and mitochondrial fusion in CRC. Naringenin combined with 5-fluorouracil significantly reduces cardiotoxicity and liver damage induced by 5-fluorouracil in nude mice bearing subcutaneous CRC tumors, and attenuates colorectal injuries in azoxymethane/DSS dextran sulfate (AOM/DSS)-induced CRC. The combination of these two drugs alters mitochondrial function by increasing reactive oxygen species (ROS) levels and decreasing the mitochondrial membrane potential (MMP), thereby stimulating AMPK/mTOR signaling. Mitochondrial dynamics are thereby regulated by activating t...