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Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition

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Τίτλος: Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition
Συγγραφείς: Choi, Hyunsung, Chun, Yang-Sook, Kim, Seung-Won, Kim, Myung-Suk, Park, Jong-Wan
Συνεισφορές: 최현성, 전양숙, 김승원, 김명석, 박종완
Στοιχεία εκδότη: American Society for Pharmacology and Experimental Therapeutics (ASPET)
Έτος έκδοσης: 2006
Συλλογή: Seoul National University: S-Space
Θεματικοί όροι: Animals, Antineoplastic Agents, Phytogenic/*pharmacology, Aryl Hydrocarbon Receptor Nuclear Translocator/genetics/*metabolism, Cell Division/drug effects, Cell Hypoxia/drug effects, Curcumin/*pharmacology/*therapeutic use, Down-Regulation/drug effects, Gene Expression Regulation, Neoplastic/drug effects, Humans, Hypoxia-Inducible Factor 1/*antagonists & inhibitors/metabolism, Male, Mice, Nude, Neoplasms/drug therapy/*pathology, Oxidation-Reduction/drug effects, Oxidative Stress/drug effects, Proteasome Endopeptidase Complex/metabolism, Protein Processing, Post-Translational/*drug effects, Protein Subunits/metabolism, RNA, Messenger/genetics/metabolism, Transcription, Genetic/drug effects, Tumor Cells, Cultured, Ubiquitin/metabolism
Περιγραφή: Hypoxia-inducible factor-1 (HIF-1), a transcription factor composed of HIF-1alpha and aryl hydrocarbon receptor nuclear translocator (ARNT), plays a key role in cell survival and angiogenesis in hypoxic tumors, and many efforts have been made to develop anticancer agents that target HIF-1alpha. However, although ARNT is also required for HIF-1 activity, ARNT has been disregarded as a therapeutic target. Curcumin is a commonly used spice and coloring agent with a variety of beneficial biological effects, which include tumor inhibition. In the present study, we tested the possibility that curcumin inhibits tumor growth by targeting HIF-1. The effects of curcumin on HIF-1 activity and expression were examined in cancer cell lines and in xenografted tumors. We found that curcumin inhibits HIF-1 activity and that this in turn down-regulates genes targeted by HIF-1. Moreover, of the two HIF-1 subunits, only ARNT was found to be destabilized by curcumin in several cancer cell types, and furthermore, ARNT expression rescued HIF-1 repression by curcumin. We also found that curcumin stimulated the proteasomal degradation of ARNT via oxidation and ubiquitination processes. In mice bearing Hep3B hepatoma, curcumin retarded tumor growth and suppressed ARNT, erythropoietin, and vascular endothelial growth factor in tumors. These results suggest that the anticancer activity of curcumin is attributable to HIF-1 inactivation by ARNT degradation.
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
Relation: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16880289; https://hdl.handle.net/10371/29608
DOI: 10.1124/mol.106.025817
Διαθεσιμότητα: https://hdl.handle.net/10371/29608
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16880289
https://doi.org/10.1124/mol.106.025817
Αριθμός Καταχώρησης: edsbas.DF5B092A
Βάση Δεδομένων: BASE
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  – Url: https://hdl.handle.net/10371/29608#
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition
– Name: Author
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  Data: <searchLink fieldCode="AR" term="%22Choi%2C+Hyunsung%22">Choi, Hyunsung</searchLink><br /><searchLink fieldCode="AR" term="%22Chun%2C+Yang-Sook%22">Chun, Yang-Sook</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+Seung-Won%22">Kim, Seung-Won</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+Myung-Suk%22">Kim, Myung-Suk</searchLink><br /><searchLink fieldCode="AR" term="%22Park%2C+Jong-Wan%22">Park, Jong-Wan</searchLink>
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  Label: Contributors
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  Data: 최현성<br />전양숙<br />김승원<br />김명석<br />박종완
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  Data: American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  Data: 2006
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  Data: Seoul National University: S-Space
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  Data: <searchLink fieldCode="DE" term="%22Animals%22">Animals</searchLink><br /><searchLink fieldCode="DE" term="%22Antineoplastic+Agents%22">Antineoplastic Agents</searchLink><br /><searchLink fieldCode="DE" term="%22Phytogenic%2F*pharmacology%22">Phytogenic/*pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22Aryl+Hydrocarbon+Receptor+Nuclear+Translocator%2Fgenetics%2F*metabolism%22">Aryl Hydrocarbon Receptor Nuclear Translocator/genetics/*metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+Division%2Fdrug+effects%22">Cell Division/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+Hypoxia%2Fdrug+effects%22">Cell Hypoxia/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Curcumin%2F*pharmacology%2F*therapeutic+use%22">Curcumin/*pharmacology/*therapeutic use</searchLink><br /><searchLink fieldCode="DE" term="%22Down-Regulation%2Fdrug+effects%22">Down-Regulation/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+Expression+Regulation%22">Gene Expression Regulation</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplastic%2Fdrug+effects%22">Neoplastic/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Humans%22">Humans</searchLink><br /><searchLink fieldCode="DE" term="%22Hypoxia-Inducible+Factor+1%2F*antagonists+%26+inhibitors%2Fmetabolism%22">Hypoxia-Inducible Factor 1/*antagonists & inhibitors/metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Male%22">Male</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Nude%22">Nude</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplasms%2Fdrug+therapy%2F*pathology%22">Neoplasms/drug therapy/*pathology</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidation-Reduction%2Fdrug+effects%22">Oxidation-Reduction/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+Stress%2Fdrug+effects%22">Oxidative Stress/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Proteasome+Endopeptidase+Complex%2Fmetabolism%22">Proteasome Endopeptidase Complex/metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Processing%22">Protein Processing</searchLink><br /><searchLink fieldCode="DE" term="%22Post-Translational%2F*drug+effects%22">Post-Translational/*drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Subunits%2Fmetabolism%22">Protein Subunits/metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22RNA%22">RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Messenger%2Fgenetics%2Fmetabolism%22">Messenger/genetics/metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Transcription%22">Transcription</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic%2Fdrug+effects%22">Genetic/drug effects</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+Cells%22">Tumor Cells</searchLink><br /><searchLink fieldCode="DE" term="%22Cultured%22">Cultured</searchLink><br /><searchLink fieldCode="DE" term="%22Ubiquitin%2Fmetabolism%22">Ubiquitin/metabolism</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Hypoxia-inducible factor-1 (HIF-1), a transcription factor composed of HIF-1alpha and aryl hydrocarbon receptor nuclear translocator (ARNT), plays a key role in cell survival and angiogenesis in hypoxic tumors, and many efforts have been made to develop anticancer agents that target HIF-1alpha. However, although ARNT is also required for HIF-1 activity, ARNT has been disregarded as a therapeutic target. Curcumin is a commonly used spice and coloring agent with a variety of beneficial biological effects, which include tumor inhibition. In the present study, we tested the possibility that curcumin inhibits tumor growth by targeting HIF-1. The effects of curcumin on HIF-1 activity and expression were examined in cancer cell lines and in xenografted tumors. We found that curcumin inhibits HIF-1 activity and that this in turn down-regulates genes targeted by HIF-1. Moreover, of the two HIF-1 subunits, only ARNT was found to be destabilized by curcumin in several cancer cell types, and furthermore, ARNT expression rescued HIF-1 repression by curcumin. We also found that curcumin stimulated the proteasomal degradation of ARNT via oxidation and ubiquitination processes. In mice bearing Hep3B hepatoma, curcumin retarded tumor growth and suppressed ARNT, erythropoietin, and vascular endothelial growth factor in tumors. These results suggest that the anticancer activity of curcumin is attributable to HIF-1 inactivation by ARNT degradation.
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  Label: DOI
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  Data: 10.1124/mol.106.025817
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  Data: edsbas.DF5B092A
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        Value: 10.1124/mol.106.025817
    Languages:
      – Text: English
    Subjects:
      – SubjectFull: Animals
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      – SubjectFull: Antineoplastic Agents
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      – TitleFull: Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition
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