Liquidambaric acid inhibits the proliferation of hepatocellular carcinoma cells by targeting PPARα-RXRα to down-regulate fatty acid metabolism.
Toxicol Appl Pharmacol
; 490: 117042, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39067772
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación hacia Abajo
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Coenzima A Ligasas
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Carcinoma Hepatocelular
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PPAR alfa
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Receptor alfa X Retinoide
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Proliferación Celular
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Ácidos Grasos
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Neoplasias Hepáticas
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China