ArticleBMC cancer2007
Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor beta dependent.
Article in BMC cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Fenretinide in cancer therapy and chemoprevention: past, present and future.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Effect of atrazine and curcumin on mouse I-10 Leydig cells: steroidogenesis and beyond.Frontiers in endocrinology · 2026Article
- Retinoids in the Pathogenesis and Treatment of Liver Diseases.Nutrients · 2022Review
- The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide.Cellular and molecular life sciences : CMLS · 2020Review
- Article
- Upregulation of retinoic acid receptor-β reverses drug resistance in cholangiocarcinoma cells by enhancing susceptibility to apoptosis.Molecular medicine reports · 2016Article
- The antitumor effect of TIG3 in liver cancer cells is involved in ERK1/2 inhibition.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Transcriptome profiling and genome-wide DNA binding define the differential role of fenretinide and all-trans RA in regulating the death and survival of human hepatocellular carcinoma Huh7 cells.Biochemical pharmacology · 2013Article
- Gene regulation is governed by a core network in hepatocellular carcinoma.BMC systems biology · 2012Article
- Detection of methylation of the RAR-β gene in patients with non-small cell lung cancer.Oncology letters · 2012Article
- ERK1/2 deactivation enhances cytoplasmic Nur77 expression level and improves the apoptotic effect of fenretinide in human liver cancer cells.Biochemical pharmacology · 2011Article
- Enrichment of Nur77 mediated by retinoic acid receptor β leads to apoptosis of human hepatocellular carcinoma cells induced by fenretinide and histone deacetylase inhibitors.Hepatology (Baltimore, Md.) · 2011Article
- Retinoid pathway and cancer therapeutics.Advanced drug delivery reviews · 2010Review
- Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells.The Journal of biological chemistry · 2010Article
- Induction and intracellular localization of Nur77 dictate fenretinide-induced apoptosis of human liver cancer cells.Biochemical pharmacology · 2010Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRetinoids are used to treat several types of cancer; however, their effects on liver cancer have not been fully characterized. To investigate the therapeutic potential of retinoids on hepatocellular carcinoma (HCC), the present study evaluates the apoptotic effect of a panel of natural and synthetic retinoids in three human HCC cell lines as well as explores the underlying mechanisms.
methodsApoptosis was determined by caspase-3 cleavage using western blot, DNA double-strand breaks using TUNEL assay, and phosphatidylserine translocation using flow cytometry analysis. Gene expression of nuclear receptors was assessed by real-time PCR. Transactivation assay and chromatin immunoprecipitation (ChIP) were conducted to evaluate the activation of RXRalpha/RARbeta pathway by fenretinide. Knockdown of RARbeta mRNA expression was achieved by siRNA transfection.
resultsOur data revealed that fenretinide effectively induces apoptosis in Huh-7 and Hep3B cells. Gene expression analysis of nuclear receptors revealed that the basal and inducibility of retinoic acid receptor beta (RARbeta) expression positively correlate with the susceptibility of HCC cells to fenretinide treatment. Furthermore, fenretinide transactivates the RXRalpha/RARbeta-mediated pathway and directly increases the transcriptional activity of RARbeta. Knockdown of RARbeta mRNA expression significantly impairs fenretinide-induced apoptosis in Huh-7 cells.
conclusionOur findings reveal that endogenous expression of retinoids receptor RARbeta gene determines the susceptibility of HCC cells to fenretinide-induced apoptosis. Our results also demonstrate fenretinide directly activates RARbeta and induces apoptosis in Huh-7 cells in a RARbeta-dependent manner. These findings suggest a novel role of RARbeta as a tumor suppressor by mediating the signals of certain chemotherapeutic agents.
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