{"title":"液甘草酸通过靶向 PPARα-RXRα 下调脂肪酸代谢抑制肝癌细胞增殖。","authors":"","doi":"10.1016/j.taap.2024.117042","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Liquidambaric acid inhibits the proliferation of hepatocellular carcinoma cells by targeting PPARα-RXRα to down-regulate fatty acid metabolism\",\"authors\":\"\",\"doi\":\"10.1016/j.taap.2024.117042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":23174,\"journal\":{\"name\":\"Toxicology and applied pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-07-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology and applied pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041008X24002400\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X24002400","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Liquidambaric acid inhibits the proliferation of hepatocellular carcinoma cells by targeting PPARα-RXRα to down-regulate fatty acid metabolism
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.
期刊介绍:
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.