2. Academic Validation
  3. The role of the natural compound naringenin in AMPK-mitochondria modulation and colorectal cancer inhibition

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

  • Phytomedicine. 2024 Aug:131:155786. doi: 10.1016/j.phymed.2024.155786.
Dan Wang 1,  Yue Zhou 1,  Li Hua 1,  Meichun Hu 1,  Ni Zhu 1,  Yifei Liu 2,  Yanhong Zhou 3
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China.
  • 2 School of Biomedical Engineering and Imaging, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China. Electronic address: liuyifei@hbust.edu.cn.
  • 3 School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China. Electronic address: zyh@hbust.edu.cn.
PMID: 38875812 DOI: 10.1016/j.phymed.2024.155786
Abstract

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 the AMPK/p-AMPK pathway, and mitochondrial homeostasis is coordinated through increased mitochondrial fusion and reduced fission to activate Apoptosis in Cancer cells.

Conclusions: Our data suggest that naringenin is important for inhibiting CRC proliferation, possibly through the AMPK pathway, to regulate mitochondrial function and induce Apoptosis in CRC.

Keywords

AMPK; Apoptosis; Colorectal cancer; Mitochondria; Mouse model; Naringenin.

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