2. Academic Validation
  3. Liquidambaric acid inhibits the proliferation of hepatocellular carcinoma cells by targeting PPARα-RXRα to down-regulate fatty acid metabolism

Liquidambaric acid inhibits the proliferation of hepatocellular carcinoma cells by targeting PPARα-RXRα to down-regulate fatty acid metabolism

  • Toxicol Appl Pharmacol. 2024 Sep:490:117042. doi: 10.1016/j.taap.2024.117042.
Xinyun Zhao 1,  Xinping Zhu 2,  Honglei Tao 3,  Hongling Zou 1,  Jili Cao 2,  Yuxin Chen 4,  Ziru Zhang 4,  Yongqiang Zhu 2,  Qun Li 5,  Mingqian Li 6
Affiliations

Affiliations

  • 1 College of Life Science, Sichuan Normal University, Chengdu 610101, Sichuan, China; Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China.
  • 2 Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China.
  • 3 Anesthesiology Department, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China.
  • 4 Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China; Hangzhou Medical College, Hangzhou, 310059, Zhejiang, China.
  • 5 College of Life Science, Sichuan Normal University, Chengdu 610101, Sichuan, China. Electronic address: liqun01234@163.com.
  • 6 Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China; Hangzhou Medical College, Hangzhou, 310059, Zhejiang, China. Electronic address: limingqian613@163.com.
PMID: 39067772 DOI: 10.1016/j.taap.2024.117042
Abstract

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. As the global obesity rate rises, non-alcoholic fatty liver disease (NAFLD) has emerged as the most rapidly increasing cause of HCC. Consequently, the regulation of lipid metabolism has become a crucial target for the prevention and treatment of HCC. Liquidambaric acid (LDA), a pentacyclic triterpenoid compound derived from various Plants, exhibits diverse biological activities. We found that LDA could inhibit HCC cell proliferation by arresting cell cycle and prompting Apoptosis. Additionally, LDA can augment the therapeutic efficacy of Regorafenib in HCC in vitro and vivo. Our study utilized transcriptome analysis, luciferase reporter assays, and co-immunocoprecipitation experiments to elucidate the anti-HCC mechanism of LDA. We discovered that LDA disrupts the formation of the PPARα-RXRα heterodimer, leading to the down-regulation of the ACSL4 gene and subsequently impacting the fatty acid metabolism of HCC cells, ultimately inhibiting HCC proliferation. Our research contributes to the identification of novel therapeutic agents and targets for the treatment of HCC.

Keywords

ACSL4; Hepatocellular Carcinoma; Liquidambaric Acid; PPARα; RXRα.

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