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Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor ß dependent
dc.contributor.author | Pengli Bu | en_US |
dc.contributor.author | Yu-Jui Wan | en_US |
dc.date.accessioned | 2009-05-05T16:13:34Z | |
dc.date.available | 2009-05-05T16:13:34Z | |
dc.date.issued | 2009-03-17 | en_US |
dc.identifier.citation | Pengli Bu;Yu-Jui Wan: Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor ß dependent. BMC Cancer 2007, 7(1):236. | en_US |
dc.identifier.uri | http://hdl.handle.net/2271/589 | en_US |
dc.description.abstract | BACKGROUND:Retinoids 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.METHODS:Apoptosis 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 RXRa/RARß pathway by fenretinide. Knockdown of RARß mRNA expression was achieved by siRNA transfection.RESULTS:Our 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 ß (RARß) expression positively correlate with the susceptibility of HCC cells to fenretinide treatment. Furthermore, fenretinide transactivates the RXRa/RARß-mediated pathway and directly increases the transcriptional activity of RARß. Knockdown of RARß mRNA expression significantly impairs fenretinide-induced apoptosis in Huh-7 cells.CONCLUSION:Our findings reveal that endogenous expression of retinoids receptor RARß gene determines the susceptibility of HCC cells to fenretinide-induced apoptosis. Our results also demonstrate fenretinide directly activates RARß and induces apoptosis in Huh-7 cells in a RARß-dependent manner. These findings suggest a novel role of RARß as a tumor suppressor by mediating the signals of certain chemotherapeutic agents. | en_US |
dc.language | en | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | BioMedCentral | en_US |
dc.relation.isversionof | http://www.biomedcentral.com/1471-2407/7/236 | en_US |
dc.relation.hasversion | http://www.biomedcentral.com/content/pdf/1471-2407-7-236.pdf | en_US |
dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0 | en_US |
dc.subject.mesh | Anticonvulsants/pharmacokinetics/ therapeutic use | en_US |
dc.subject.mesh | Attitude to Health | en_US |
dc.subject.mesh | Communication | en_US |
dc.subject.mesh | Drugs, Generic/pharmacokinetics/ therapeutic use | en_US |
dc.subject.mesh | Epilepsy/ drug therapy/psychology | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Patient Education as Topic | en_US |
dc.subject.mesh | Patient Satisfaction | en_US |
dc.subject.mesh | Physician-Patient Relations | en_US |
dc.subject.mesh | Therapeutic Equivalency | en_US |
dc.title | Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor ß dependent | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1186/1471-2407-7-236 | en_US |
dc.identifier.pmid | PMC19292903 | en_US |
dc.rights.accessrights | openAccess | en_US |
dc.date.captured | 2009-04-27 | en_US |
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Except where otherwise noted, this item's license is described as: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.